While many villains in the Resident Evil franchise trend towards Tragic Monster, or are simply too inhuman to pass moral judgement on, there are these major exceptions, who prove that Humans Are the Real Monsters.
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- Albert Wesker is a self-serving, high-ranking member of Umbrella Corporation and the favorite pupil of Dr. Oswell E. Spencer. Helping out with assassinations and covering up the incidents, Wesker also conducts his own experiments along the way. After Dr. Marcus attempted to spread his virus, Wesker decided to leave Umbrella, and follows up with his plan to lure both Alpha and Beta S.T.A.R teams to the mansion, where he would have them killed one by one and retrieve the samples of T-002 Tyrant to give them to a rival organization in exchange for a new job. Resurrecting himself with the T-002 virus after being killed by Tyrant, Wesker obtained superhuman strength and speed and started working for the Organization and led an attack on Rockfort Island, causing countless deaths, solely so he could get his hands on the T-Veronica virus. Leaving the Organization for TRICELL Inc., Wesker personally led the experimentation on thousands of people, before he created the new virus, called Uroboros, with which he infected the whole city of Kijuju and many tribes, that surrounded it, transforming the residents into the mindless zombies. Planning to spread Uroboros across the world, Wesker desires to kill billions, solely so he could become a god.
- Resident Evil 2: Raccoon City Police Chief Brian Irons is monstrous in both the original game and the 2019 remake:
- Original: Irons was accused of raping a university student several times, before getting away with it and becoming Chief of the Raccoon City Police Department. Taking bribes from the Umbrella Corporation and allowing them to conduct experiments on the city's citizens, he would use said bribes to fund his own personal "Taxidermy Sex Dungeon of Evil", filled with bones, surgical tools, acids, and stuffed bodies. When Umbrella's T-Virus breaks free and spreads throughout Raccoon City, Irons decides to use this opportunity to cause chaos and kill people, which includes zombies, innocent bystanders, fellow cops, and the mayor's daughter. Horribly depraved, Irons proves you don't need superpowers or grandiose schemes to be horrifically evil.
- REmake: Irons is secretly working for Umbrella. A raping, murderous human taxidermist, Irons prefers killing women and having their bodies converted into stuffed dolls for him to admire. Moonlighting as the city's orphanage director, Irons, under Umbrella's orders, has hundreds of children painfully experimented on for the Birkins' scientific research, with most of the children dying. When one of the children manage to escape, Irons has Umbrella soldiers execute every child at the orphanage to cover the company's tracks.
- 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. Running the Umbrella training facility in the Arklay Mountains, Marcus subjected at least 20 people to experimentation with the T-Virus, resulting in their deaths. After being assassinated by Umbrella CEO Ozwell Spencer, he was resurrected when his memories and consciousness were absorbed by his most recent creation, the Queen Leech. Desiring revenge against Umbrella, 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.
- Resident Evil 4: Osmund Saddler, the master of Los Illuminados ("The Enlightened Ones"), reawakens the Las Plagas parasites, infecting multiple villagers before determining the strain works. Injecting himself with a "master" Plaga, 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 leaving them as broken shells for him to control while Saddler reigns over the world.
- Resident Evil 6: Derek Clifford Simmons is the National Security Advisor to President Adam Benford and the one behind the nuclear destruction of Raccoon City. Serving as the Arc Villain for Leon's campaign, Simmons uses the C-Virus to cause the zombie outbreak in Tall Oaks, the place where the President plans to reveal the truth about Raccoon City and the Bio Organic Weapons trade to the world, causing 70,000 casualties. He also forces Secret Service Agent Helena Harper to personally infect the President by holding her sister hostage, threatening to turn her into a B.O.W.; he does so anyway, and frames Helena and Leon for his crimes. Also apart of said B.O.W. trades, he oversees the creation of said C-Virus by subjecting Sherry Birkin to constant experimentation. Simmons also has an obsessive lust for Ada Wong, and when she rejected him, he would use the C-Virus to create a "perfect Ada Wong", experimenting on 12,235 women, with only one, Carla Radames, surviving, causing her Start of Darkness. Finally confronted by Leon and Helena, Simmons tries to justify his actions, only to be called out on his excuses, revealing Simmons to be nothing more than a perverted madman willing to cause needless death just to hold on to his position in power.
- Resident Evil 7: Biohazard: Lucas Baker, the Big Bad of the Not A Hero DLC, was known as the "Bad Seed" of the Baker family. A brilliant, yet sociopathic, inventor who once trapped a childhood bully to starve to death in the attic, Lucas liberated himself from Eveline's control but found he enjoyed his new powers and ability to "cut loose"—regularly capturing others and putting them in his death traps to test them out, Lucas also makes sure it's impossible to escape the traps so even if one solves them, they'll still die painfully. When Chris Redfield goes in, Lucas captures three of his soldiers and has Chris experience their deaths before trying to kill Chris as well. A complete sociopath with no regard for anyone, even his own family, Lucas is a unique glimpse at a twisted, inventive Serial Killer in the world of Resident Evil.
- Gun Survivor: Vincent Goldman is the commander of Sheena Island on the behalf of the Umbrella Corporation and responsible for creating the Hypnos T-Type Virus. He creates the virus by kidnapping children and torture them for days by extracting the hormone from their skulls while they are still alive and fully conscious. When the children try to escape the island, Goldman proceeds to kill them all and unleash The Virus on the entire island when its populace rebels.
- The Darkside Chronicles: Alexia Ashford no longer has love for her brother as a part of her personality, the way it was in Code: Veronica, and her evil is cranked up a few notches higher. 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 father, tortured a classmate to death (and recorded the session) 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. 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 and forces him to fight her to the death, and tries repeatedly to kill Chris and Claire for no other reason than their presence is 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.
- First film: Percival Spencer "Spence" Parks is a member of Umbrella Corporation's security force and the one responsible for the outbreak. Overhearing his lover Alice and an activist planning to expose Umbrella's illegal activities by stealing the T-Virus, Spence decided to steal the virus himself and sell it on the Black Market so that he and Alice can spend the rest of their lives in luxury. To prevent the theft from being discovered, Spence purposely causes an outbreak inside the laboratory so that the A.I. system puts the whole place under lockdown and kills the whole staff. Having temporarily lost his memories as the side effect of a knockout gas, he's found by a squad of Umbrella soldiers sent to investigate the incident. Eventually, his memories return, and he holds the remaining survivors at gunpoint, while trying to convince Alice to join him. When she refuses, Spence locks them up and leaves them behind to die, showing that he cared more about the money than about his lover.
- Apocalypse: Major Timothy Cain is the Umbrella operative in charge of containing the viral outbreak in Racoon City. When a zombie almost escapes the city, Cain closes the gates, having his men fire on the crowd to force them back into the city. Cain then releases the Nemesis, a bioweapon he created from Alice's friend Matt, into the city, having it kill the members of S.T.A.R.S. as a test. Interested in testing Alice's capabilities as a weapon against Nemesis, Cain murders Charles Ashford to force her to fight it, threatening to kill the rest of her friends, including Charles's young daughter. When his cruelty causes Nemesis to turn on him, Cain orders Umbrella to nuke Racoon city, abandoning both Alice and Nemesis to save his own skin.
- Extinction: The first clone of Dr. Alexander Isaacs, while created to serve Umbrella, was too vile and egotistical to control. Isaacs experimented on clones of Alice, putting them through sadistic tests that resulted in 87 of them dying. He injects zombies with the blood of the Alice clones, resulting in them becoming stronger and attacking him and his fellow scientists, who Isaacs leaves to die. Hoping that the real Alice's blood will domesticate the zombies, Isaacs attacks Claire Redfield's convoy with enhanced zombies in order to kill Alice, killing many people including Carlos Olivera. After being bitten by an enhanced zombie, Isaacs mutated into a monster and slaughtered everyone in his facility, betraying Umbrella for his own dark ambitions.
- Albert Wesker is a high-ranking member of the Umbrella Corporation and Dr. Alexander Isaacs's chief subordinate. Years ago, Wesker murdered the kind-hearted Dr. Marcus for Isaacs and aided Isaacs in his unethical experiments. When Isaacs plans to release the T-Virus to kill all of humanity except his chosen few, Wesker agrees to run Umbrella while the rest are cryogenically frozen. When Alice and her clones attack Wesker's Tokyo facility, he floods parts of it with neurotoxin, murdering his subordinate for pointing out that this will kill his own men, and blows up the entire facility, killing everyone inside. Wesker leads survivors to The Arcadia, pretending that it's a safe haven from the infection, so he can experiment on them with mind-altering chemicals. After injecting himself with the T-Virus, Wesker turns to cannibalism to maintain control of himself. After failing to eat Alice, Wesker consumes his loyal subordinate and attempts to destroy the Arcadia and the countless people on it. When Alice is kidnapped by the Red Queen, Wesker sends a team to save her and destroy an Umbrella facility filled with clones. Wesker posed as well-intentioned in order to lead Alice, his own team, and countless others into a trap that killed everyone but Alice. Wesker then organizes attacks on the last survivors on Earth, and personally kills Alice's allies when they try to release the antivirus.
- The Final Chapter: Dr. Alexander Isaacs, the Big Bad of the film 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. Isaacs ran simulated outbreaks with sentient clones in order to sell the virus to superpowers. Later gaining delusions of godhood, Isaacs opted to release the Virus at large while freezing himself and the few "chosen" in cryogenic hibernation in order to later rebuild the world in his image. The end result was a mass extinction event of the world and the death of most of humanity. Isaacs leaves his own clones and Albert Wesker to clean up, aiming to exterminate any survivors. When he awakens, Isaacs attacks the heroine Alicia "Alice" Marcus, tauntingly revealing that she's a clone and slicing off her fingers before trying to murder her, intent on maintaining the ultimate power he's betrayed and murdered to achieve.
- Biohazard: The Wicked North Sea Light Novel, by Kyū Asakura: Countess Mylène Beardsley is the seventeenth head of the prestigious Beardsley family and a woman with an immense superiority complex. An enhanced human, Mylène constructed a laboratory under her castle to conduct unnecessary experiments on villagers and her servants. Having infected Kate with the Neo T-Virus, Mylène tries to trick Rain into consuming a soup with human eyeballs. In an act of rebellion against Umbrella, Mylène broke her experiments out of containment and released a nerve gas on her own guests. Fancying herself as a being "superior in everything from brain to appearance", Mylène's ultimate goal was to stand at the top of Umbrella and control the world. A rich, teenaged low-functioning psychopath whose methods were questioned by Umbrella itself, Mylène was an example of how dangerous sadism and narcissism can be if combined in one single person.
- Biohazard 2 manhua:
- The man only known as "God" is the president of the Umbrella Corporation who desires the destruction of the world by any means necessary. Unleashing the G-virus onto Raccoon City and turning everyone into zombies, he uploads his brain into a parasite once news of Chris Redfield storming his headquarters arrives, and orders his staff members to commit suicide. Retreating to the artificial islands, he sets up a cyborg gladiator ring and unleashes a poisonous gas onto the entire audience once he's been found by the BHST. Taking control of his supposed friend, Inzaghi, he sends his squad to infect multiple parts of the island with his virus, infecting countless innocents. Having kidnapped Leon's father and making him the terrorist assassin known as the Hardened War General, he orders him to infect multiple parts of the island with the G-virus, including Leon himself. Taking BHST prisoner, he reveals that he had cloned the deceased Ada Wong to be his bride, ordering her to kill Leon and herself when the former arrives to stop him. Duking it out with Leon, he destroys an entire city while looking for him, and combines with him to become the ultimate life form, where he attempts to nuke the world to achieve his dreams of an apocalyptic wasteland.
- Brian (Irons), like his game counterpart, is a violent rapist secretly working for Umbrella. As a child, he would capture rabbits and dissect them for fun. Using his position as Commissioner of the Raccoon City Police Department, he shuts down STARS after the Spencer Mansion incident to cover Umbrella's tracks and leads the massacre of several Umbrella scientists in order to take out William Birkin. Ordered to keep Amy Chan safe, he instead kills her and plans to keep her as a trophy. Capturing Claire Redfield, he shows her his room containing stolen human organs—hoping to add hers to his collection—and has Leon thrown into a room with Lickers.
- Biohazard 3: Last Escape & Supplemental Edition manhua: "Boss" is a senior executive at Umbrella placed in charge of the T-virus program. Capturing innocent people and having their families murdered, Boss transforms these people into Tyrants, seeking to expand on William Birkin's scientific studies. When one of his scientists, Leo, tried leaving Umbrella, Boss had his friends murdered and imprisons him for decades. Once Nemesis/The Sniper invades Umbrella headquarters, Boss casually lets his cohorts get killed and escapes in a helicopter. Seeking to make more profit, Boss decides to clone various people and sell them for money, ordering Claire's death once he's been found out.
- Resident Evil Vol. 2 comic, by Ricardo Sanchez et al: Neuermann Giesel is a T-Virus-enhanced clone of Arms Dealer, Fritz Giesel, created by Fritz to help him run Giesel Industries. Fritz places Neu in charge of developing black market Bio Organic Weapons, which Neu creates by painfully transforming the residents of numerous Übelandian towns into monsters whose abilities he showcases to a Uradorian warlord by having the creatures massacre various villages along the border of Übelandia and Urador. Neu also arranges for viral specimens to be exposed to cosmic radiation, which results in deadly outbreaks on both a space station and in Grezbekistan. When the Bioterrorism Security Assessment Alliance begins investigating Giesel Industries, Neu has his "pet" monstrosities slaughter several members of the BSAA team sent to search the Giesel Estate, whose domestic staff Neu abandons to die in the carnage while he escapes to his BOW factory in Urador. Neu tries to starve the pursuing BSAA agents of reinforcements and supplies by overrunning all nearby towns and BSAA bases with zombies, and when the agents try to blow up his factory, they discover that Neu has designed it with a Dead Man's Switch that will cause pockets of BOWs that are hidden throughout the major population centers of Übelandia to activate and rampage, dooming the country and potentially all of South America. After the agents manage to thwart the switch and destroy the factory, Neu makes one final attempt to kill them by mutating into a Tyrant.
- Resident Evil: Degeneration: Dr. Frederic Downing, a member of WilPharma, is the one behind the events of the movie. Previously a scientist for Umbrella Corps who stole samples of the t and G-viruses before Raccoon City's annihilation, he planned to sell them and a vaccine through the black market as controllable, profitable bioweapons, later unleashing them on various countries as a way to pitch them to potential buyers. Finding a buyer in the form of General Miguel Grandé, he unleashed the t-virus onto Harvardville Airport that resulted in a zombie outbreak, blew up several vaccine trucks to disguise the incident as a terrorist attack, blew up a WilPharma building to kill Claire Redfield, and injected Curtis Miller with the G-virus, all as a way to create a pitch video for Grandé.