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Chris Redfield: Excella...what's going on!?
Excella Gionne (in inexcrutiating pain from Uroboros) : Why—when I've done so much—all for you—
Albert Wesker: Don't worry, your mission is at its end. Uroboros is on the eve of its appearance. Six billion cries of agony will birth a new balance!
Excella: Albert...you said we'd change this world together—why!?
Sheva Alomar: I thought they were partners.
Chris: Wesker doesn't give a damn about anybody but himself.
Wesker: Unfortunately, it's too late for you. You will not live to see the dawn! Sorry Excella, but it appears Uroboros has rejected you.
(Excella is now on her knees, shouting in pain, and transforms into a tentacle monster).
—Resident Evil 5
While many Resident Evil villains trend towards Tragic Monster, or simply being too inhuman to bother passing moral judgement on, there are major exceptions who prove that Humans Are the Real Monsters.
- Albert Wesker. This man is, when you look at the big picture, responsible for everything bad that happens in the series' canon, and the most irredeemably evil villain in the series. A major sufferer of Chronic Backstabbing Disorder, he does not care for the well being of his "partners", and will gladly dispose of them when the time comes that they are no longer of use to him. First off, after becoming the commander of the S.T.A.R.S Alpha Team (we later learn he was planted as a Double Agent), he traps his crew inside of a secret Umbrella facility disguised as a mansion, and uses his "teammates" as test subjects for his grotesque experiments, killing more than half of them in the process. He was also partially behind the tragic backstory of William Birkin, the Big Bad of Resident Evil 2, as they were actually colleagues. Later, he finds out about Spencer manipulating and engineering him to be who he is today, and is none too pleased, killing him in the process, as well as taking down series mainstay Jill Valentine to their supposed deaths. Surviving the fall, he decides to brainwash Jill into becoming his slave, mainly being petty against his nemesis Chris Redfield. He then goes on to kill U.S. Senator Ron Davis in Degeneration after considering him a liability to his new company Tricell. Then, he decides to pit Jill against Chris just for his own amusement in watching Chris' torment in fighting his partner. Then, he betrays Excella Gionne, his then-partner and one-sided lover, in the most cruel way imaginable - calling her a failed experiment, injecting her with his Ouroboros virus, and sending her out to deal with Chris and Sheva while he escapes on his own. And his motivation for doing all of this? To become God of the New World by infecting every single human on the planet with his Ouroboros virus, which will kill those with unworthy DNA and leave only the chosen few for him to rule over. When he was finally confirmed dead by Word of God (getting burned alive in a volcano and then getting his head exploded via dual Rocket Launchers, in the most extreme No One Could Survive That moment the series has ever seen), fans rejoiced.
- Brian Irons first establishes himself as an irredeemable scumbag during his university days when he raped a fellow student. Due to being an "outstanding excellence in academics" however, he managed get away with it and later became The Chief of Raccoon City Police Department, where the Umbrella Corporation would bribe him to turn a blind eye they perform there experiments on the City's citizens. Not only would gladly accept these bribes but he would use them to fund his own personal "Taxidermy Sex Dungeon of Evil" and use it as a place to lure his victims, male and female, where he would rape them before killing them. He would then stuff their corpses and displaying their bodies, so he can admire them. When Umbrella's T-Virus broke free, spreading throughout Raccoon City, causing massive chaos, he decides to use this opportunity to kill whomever he wants ranging from zombies, innocent bystanders, fellow cops, and even the mayor's daughter. When he finds Claire Redfield, he takes her to his hideout where he attempts to rape and kill her, while promising to do the same thing to Sherry, a child. While lacking the vast resources, grandiose visions, and god complexes that many other villains have, he makes up for it with meaningless cruelty and human depravity.
- Osmund Saddler, master of Los Illuminado in Resident Evil 4, reawakens the Las Plagas parasites, infecting multiple villagers before determining the strain works. Injecting him with a 'master' Las Plagas, Saddler spreads the parasite to the rest of the village, destroying the minds of everyone it comes into contact with and leaving them as Saddler's puppets. Saddler also conducts horrible experiments on those in his clutches and disposes of the corpses by feeding them to Las Plagas infected monsters. However, when children are infected they die painfully due to their bodies not being developed enough to handle the strain. Saddler plans to use the President's daughter to infect her father and from there take over the US and then the rest of the world, infecting everyone with Las Plagas and leave them as his slaves while Saddler reigns over the world.
- Lucas Baker from Resident Evil 7, who unlike his parents, is NOT under Eveline's control. Initially a juvenile delinquent (in contrast to the rest of his family, who are good people) who is implied to have murdered a bully in his youth, Lucas also happened to be a genius inventor. When Eveline took control of his family and he was cured of her control, Lucas realized that he could do whatever he wanted to the people his family abducted without fear of repercussions, and proceeded to play sadistic games with his victims that led to their deaths. When Chris Redfield is sent to hunt him down, he proceeds to murder his soldiers that had also been sent to tail him, before eventually being killed by Chris.
- The Big Bad of Resident Evil 0, Dr. James Marcus was one of three co-founders of Umbrella Corporation and a mad scientist without regard for anyone or anything unlucky enough to get in his way. In the late 1960s, Umbrella CEO Ozwell Spencer assigned Marcus to head the company's recently-constructed research center in the Arklay Mountains, which would also be used as a management training facility. Dr. Marcus seized the opportunity to use several of the trainees sent to him as test subjects for the newly-created T-Virus, which he himself had developed in his lab by mixing the Progenitor Virus with leech DNA. At least 20 people were unwittingly subjected to his experiments, all of whom died and were either sent off to other laboratories for further research or dumped into the nearby sewers. In 1988, Spencer had Marcus assassinated following a decade-long schism between them; however, he was resurrected ten years later when his memories and consciousness were absorbed by his most recent creation, the Queen Leech, which had the ability to control other T-Virus leeches. Through the Queen Leech, Marcus set out on his goal to exact revenge on Umbrella. To do so, he leaked the T-Virus under the Spencer Mansion and on the Ecliptic Express, killing dozens of people and partly precipitating the crisis that led to the contamination of Raccoon City itself. He had every intention of causing large-scale destruction - when Rebecca and Billy finally encounter him, he gleefully expresses his desire to destroy the entire world. Callous and amoral, Dr. Marcus's complete lack of humanity predates his transmutation into a literal monster, which merely gave him the means to demonstrate the true and terrifying extent of his depravity.
- In Resident Evil Gun Survivor, Vincent Goldman serves as the commander of Sheena Island on the behalf of the Umbrella Corporation and was in charge of creating the Hypnos T-Type Virus. He would use this position to kidnap children all over the world and torture them for days to secrete the hormones needed for the virus. He would then extract the hormone from their skulls while they are still alive and fully conscious. When the surviving children attempts to escape the island, Goldman proceeds to callously shoot them upon finding them. This action caused a rebellion within the island inhabitant where he proceed to unleash his lethal virus on to populace out of spite. Vincent Goldman was so vile that even Umbrella was disgusted by his cruelty.
- Commissioner Morgan Lansdale from Resident Evil: Revelations is the head of the Federal Bioterrorism Commission, and eventually revealed to be the main architect behind the destruction of the city Terragrisia, responsible for deaths in hundreds if not thousands all to obtain good publicity. He supplied the Italian terrorist organization Il Vetro ("The Greyhound") with Bio Organic Weapons and the T-Abyss Virus to unleash onto Terragrisia while giving them the ship Queen Dido as their base. The chaos consuming Terragrisia allowed him to obtain clearance to use Regia SOLIS to obliterate the man made island with all survivors still on board. With no further use of Il Vetro, he detonates the ship they are still on along with the Virus, causing all the members to turn into blob monsters. He also sends researchers onto the other ships, Queen Zenobia and Queen Semiramis, to work on a sellable vaccine for the virus, only to unleash B.O.Ws and the virus onto the ships to dispose of them once he had what he needed. Upon finding out that BSAA agents Jill Valentine, Parker Luciani, and later Chris Redfield are aboard the Queen Zenobia, he tries various methods to kill them by blowing up the ship, ranging from using Regia SOLIS to having his mole Jessica Stewart detonate the ship despite knowing all of that will cause the virus to spread and infect 1/5th of the world's oceans. When finally exposed, Morgan Lansdale tries to justify his actions, only for BSAA director Clive R. O'Brian to retort his attempts, showing that Lansdale is nothing more than a backstabbing hypocrite willing to destroy everything and everyone in his path just to keep his self-image.
- By the time of Resident Evil: The Darkside Chronicles, Alexia Ashford no longer has any love for her brother, unlike in Code: Veronica, and instead, her evil is cranked up a few notches higher than before. A Child Prodigy who joined the Umbrella Corporation at the age of twelve, Alexia was also an entitled sadist with a serious god complex. She aided her brother in murdering and experimenting on their own father, tortured a classmate to death (and recorded the session) just for being almost as smart as she was, and eventually injected herself with the T-Veronica virus, which she planned to use to Ascend to a Higher Plane of Existence. Having been reawakened from cryogenic sleep in her twenties, Alexia kills her brother for not waking her up on time, transforms Claire Redfield's Love Interest, Steve Burnside, into a monster. forcing him to fight her to the death, and repeatedly tries to kill Chris and Claire for no other reason than their mere presence at her facility. She reveals that her plan is to infect the world with the T-Veronica virus, enslaving most of humanity to her will. When asked why, Alexia just gloats about how, as a superior specimen of humanity, she deserves to be queen.
- Dr. Alexander Isaacs, the Big Bad of The Final Chapter and the Greater-Scope Villain of the entire series, is an Evil Genius who murdered his kindhearted colleague Dr. Marcus for the T-Virus when he realized its potential as a weapon. Experimenting on the innocent, Isaacs later gained delusions of godhood and opted to release the Virus at large while freezing himself and the few "chosen" in cryogenic hibernation in order to rebuild the world in his image later. The end result was a mass extinction event of the world and the deaths of most of the human race. Isaacs leaves his own clones to clean up, aiming to exterminate any survivors. When he awakens, Isaacs promptly attempts to kill the heroine Alicia "Alice" Marcus as well, intent on maintaining the ultimate power he's betrayed and murdered to achieve.