Advance Wars had Lash, a girl genius version of the mad scientist. The reboot Days of Ruin has Caulder/Stolos, probably the most extreme mad scientist ever. Among his creations are the games equivalent to nukes, a giant bomber, cloned humans intended to be used as Super Commanders, and most of all, a virus that kills its host by growing flowers all over its body. He also loves to manipulate people into fighting each other just so he can observe them and views humans as little more than test subjects... Including himself.
He doesn't think that the flower virus is deadly enough, so he UPGRADES it to kill EVERYONE (rather than just children, which is what the first version did). Also, 'Giant Bomber' means a plane so large that two armies can fight on one wing, and each bomb can destroy thirteen buildings in one explosion. Guy is a genius. Completely insane nutcase, but still a genius.
Dr. X from AVirusNamedTOM. He says it best himself in the intro movie:
Klungo from the Banjo-Kazooie games. He's responsible for Gruntilda's Beauty-Stealing Machine and in Grunty's Revenge is hinted that he also created Grunty's monster army. Unique in the fact he also happens to be the The Igor.
Dr. Suchong from BioShock is the sinister and detached version, the warped genius behind much ADAM research, including several plasmids, the Little Sisters, and the Big Daddies. He was the linchpin behind virtually everything that went wrong in Rapture, including the protagonist himself — but, at least, he died an ironic death...
Busuzima from Bloody Roar went so far as to freakishly mutate his co-worker Stun to steal his research. Starting as a child who wanted to create a creature that would never die, he's fallen to become a Jerkass who would sacrifice anybody for money and power. He can also turn into a chameleon and fight quite well, but (unusually for his occupation) that's a natural part of him.
City of Heroes and City of Villains have several of these, not including player character concepts: Dr. Aeon is the foremost example, tapping the energy of a slumbering demon in order to power his city. There's also Vernon von Grun, a Mad Scientist-In-Training Lab Assistant.
The Clockwork King thinks that he's a Mad Scientist, but he's actually an extremely powerful psychic whose creations work because he believes they do.
Brutally expanded on in a high level story arc, where an alternate universe version of the Clockwork King has realised his own sanity, and focused enough to conquer the entire planet and kill everyone on it.
The Council, of which all of The Center's generals are mad scientists (SIX of them!). The lower ranks of the Council are filled with their creations.
It's mentioned at least once that Arachnos (the Big Bad Organization ruling the isles in which the game takes place), intentionally trains and recruits mad scientists, in order to stay ahead of the mad science game, ensuring their dominance above lesser criminal organizations.
Every single villain in the Crash Bandicoot franchise is either a mad scientist (usually with a first name starting with the letter N, which lends itself to Punny Names such as Neo Cortex (the usual megalomaniac Big Bad), N.Gin (the Yes-Man and more recently, The Igor), Nitrus Brio (a chuckling Frankenstein-like midget), N.Tropy, N.Oxide and N.Trance) or a hideously mutated anthropomorphic animal created by said mad scientists.
Mao in Disgaea 3. Despite being the main character, Mao is quite possibly the archetypal mad scientist. Thoughts of experimentation on interesting subjects send him into an excited fit, even if the subject turns out to be himself. The main story ends with Mao capturing and continually experimenting on the Big Bad, instead of killing him.
Disgaea 4 introduced the Professor class. One of her personality types is even called "Mad Scientist".
The first one, Terrance Kyne, while he's gone a bit batty after being thrust into the middle of a Zombie Apocalypse, and has a habit of talking to his late wife (although that's not a sign of mental illness, it's a manifestation of the Marker), he's an OK sort who just wants to help Issac.
Nolan Stross from Dead Space 2 was also a scientist. In the prequel movie Aftermathhe is exposed to a shard of the Marker and incidentally causes most of the crew of his ship, the O'Bannon, to get killed by Necromorphs. He also murders his wife and infant son in a fit of hallucinations. He's institutionalized on the Sprawl, and links up with Isaac and Ellie; at first he's somewhat lucid and wants to destroy the marker, but as the game goes on, his hallucinations worsen, and becomes violent, gouging Ellie's eye out. He later tries to murder Isaac, who kills him in self-defense.
Bob Page from Deus Ex certainly fits this trope. The man has built multi-national conglomerates dedicated to such "grey area" pursuits as transgenics, bioweapons, espionage, nanotechnology, and cybernetics; all an Evil Plan to rule the world.
Bob Page also employs plenty of other scientists, some of whom are completely ignorant about what they're doing, some of whom were captured and forced to work and some of whom are just completely without morals.
Dr. Neurosis in Brain Dead 13, who plays out every Mad Scientist trope in the book.
At least three Devil May Cry villains have been scientists researching, experimenting on and trying to create demons — Arius in Devil May Cry 2, Agnus in Devil May Cry 4 and Chen from the second novel. It's debatable as to how "scientific" this line of work is, though, so we could call them Mad Pseudoscientists or something.
Professor Monkey-for-a-Head from the Earthworm Jim games. "Don't make the monkey mad, son!"
The Master from Fallout, who beneath a calm, arrogant exterior topped by the reasoning of a Well-Intentioned Extremist exhibited a multiple personality disorder and overall emotional frailty.
The Fallout 3 DLC Point Lookout gives us Professor Calvert, a Brain in a Jar with a robot filled underground base whose goal is to turn all of Point Lookout's inhabitants into his mind controlled slaves.
The main game gives us Dr. Stanislaus Braun, a Vault-Tec scientist who created an advanced simulation program that he subjected the population of Vault 112 to, torturing and killing them in different ways and bringing them back with the technology at his hands.
The Fallout: New Vegas DLC Old World Blues has the Think Tanks, Pre-War scientists who chose to make themselves floating Brains In Jars whose stated goal is For Science!. It also doesn't help that they do a lot of drugs on their own free time.
Played straight and then subverted by Dr. Mobius, who plays the stereotypical mad scientist bent on domination and revenge with science but it then turns out *he* is the responsible one (sort of) who's role is to keep the other scientists who are actually far worse than him in check.
Final Fantasy IV gives us Dr. Lugae, one of Rubicante's servants. He gleefully turned Edge's parents into hideous monsters, and when the party confronts him attacks them with a giant robot named Barnabas before turning into a mechanical skeleton to continue the fray. When the heroes finally reach Rubicante, he actually apologizes for Lugae's actions.
Hojo from Final Fantasy VII is truly an archetypal Mad Scientist, right down to his outfit and sociopathic habit of sacrificing a great deal for the sake of scientific discovery (which, in his case, underlies his utter insanity). When you get down to it, Hojo may very well be the leading villain in the game, considering that most of the conflict in the game is indirectly his fault.
Final Fantasy XII subverts this with its own Cid. He works for the Archadians to manufacture their Nethicite, lurks in the forbidden and dangerous Draklor Laboratory doing no-one-wants-to-know manner of experiments with Magitek and his first scene shows him walking down a hall talking to himself with a Motor Mouth before apparently noticing Vayne out of nowhere and having a normal conversation with him. However, he's perfectly sane and is exactly aware of what he's doing. The things he studies are just particularly fascinating and important fields to research, he just enjoys being a Large Ham for the fun of it, and he's not actually talking to himself, he's talking to Venat, the Man Behind the Man that for most of the game is invisible to all but Cid. As a whole, like the rest of XII's villains he's revealed as a Well-Intentioned ExtremistAnti-Villain once the details of his backstory and personality become clear.
Kefka Palazzo may qualify as one from Final Fantasy VI, seeing how it was heavily implied that Kefka's the one who invented Terra's Slave Crown.
Dr. Curien in the House of the Dead series. The third game has little cutscenes that chronicle his transformation from "scientist-trying-to-find-cure-for-sick-son" to "zombie-obsessed-psycho."
The first six members of Organisation XIII in Kingdom Hearts II were originally assistants to Ansem the Wise and his research on the Heartless. Vexen keeps up his research.
Arguably, Xehanort from Birth by Sleep is also one. He tries to restart a war that destroyed all worlds. FOR SCIENCE!!!!
And Braig, Dilan, Aeleus, and Ienzo either, considering what happened when they went just a liiiiiittle too far trying to make sense of Darkness in the heart...
Doctor Fred Edison from Maniac Mansion, its sequel Day Of The Tentacle, and the television program arguably based on them. Granted, his desire to take over the world and generally be evil was planted in his head by a purple meteor, but as the sequel shows, even when he's not being controlled, Fred is still a very whacked-out and amoral scientist.
The second game's problems stem from a machine built by the Doc whose only purpose is generating massive amounts of toxic waste. Why? Because the other mad scientists were making fun of him for his inventions being too environment-friendly. That must've been after he dismantled his nuclear reactor chilled by a swimming pool.
Dr. Albert Wily from the Mega Man series; arguably, the heroic Dr. Light as well.
Wily's so nuts, some of his own creations are mad scientists, too; most notably, Gravity Man, whose data card quote is taken from Galileo.
And Wily's also notable in that he's one of the few villainous Mad Scientists whose overall plans actually end up succeeding, albeit posthumously. When you remember that Wily created Zero and infected him with the original strain of the Maverick Virus, and it was that same virus that transferred to Sigma during his first battle with Zero, thus kicking off the Maverick Rebellion, and it was that rebellion that basically kicked off the events of the rest of the Mega Man continuity (barring Battle Network and Star Force, which are an alternate continuity), effectively making him the Bigger Bad of the entire series, you've got one effective Mad Scientist on your hands.
Any and every scientist working for Umbrella in the Resident Evil series is virtually guaranteed to be a Mad Scientist. The majority of the games in the franchise have also had a batshit insane researcher as the Big Bad:
Overall series? Besides Wesker, we also have Spencer, who was originally a scientist who worked on the Progenitor Virus.
Guildernstern from the Onimusha series of videogames, and his successor in the fourth installment Rosencrantz (see a pattern here?), both qualify as mad scientists. Guildenstern can't help but experiment with demon and human anatomy to come up with truly horrifying monsters for the protagonist to face. Even in the second game where he is never seen, he is mentioned in many in-game texts as the reason your character has to go through such hell with biomechanical demonic constructs plaguing him at every other turn.
In Psychonauts, the villain Dr. Loboto has all the trappings of a mad scientist, while using the style of his doubtless-failed career in dentistry.
Sasha Nein is a rare good example.
Sasha: Now, just relax. You won't feel a thing. Unless something really very bad happens.
Also, Word of God states that he experimented on himself, infusing monster cells into his own, extending his own lifespan, however he is still mortal regardless.
Mad Scientist: Von Frog II in the Something series. He's smart enough to build a tank and an UFO, but he went out of his way to attack a helpless village of bears.
Dr. Ivo "Eggman" Robotnik from the Sonic the Hedgehog series. He has a recorded IQ of 300 and an almost admirable level of persistence. He is, however, entirely sane, relatively speaking.
Also Eggman's grandfather, Gerald Robotnik, brilliant scientist who designed a working orbital space colony and dabbled with artificial life forms among other things. He was driven insane after his granddaughter was killed by G.U.N.. The depths of his hatred for the world and his desire to destroy it shocked even Eggman himself.
Andross in Star Fox, who employed several bio-weapons (as in, lifeforms created as weapons) in Star Fox64 and Command. The later however somewhat redeems his actions by revealing that he had been working on a device that would terraform the aptly named planet Venom into a more inhabitable one. Which just happens to be the perfect counter to the new threat, which come from the acidic oceans of the planet. However, the same game also hints that he was the one who created the new threat in the first place in the Good Bye Fox scenario.
Also from Super Robot Wars, Aguila Setme and Egret Fehu. Both are similar to Lemon, except she at least had human decency and Alas, Poor Villain. Aguila mind fucks CHILDREN and turns them in living weapons, and figures any psychological scarring her sick experiments inflict can simply be removed with more brainwashing, or retained in some form if it make them fight even better. Egret builds Artifical Human Machinery Children, who agree with his belief Humansare Bastards (and we suck from a biological standpoint), and is willing to kill all of humanity to achieve his end goals.
Kenzo Kobayashi was one of these (still is to an extent), but performed a Heel-Face Turn in Original Generation (officially, was doing so slowly anyway after he developed a conscience prior)
Dr. Bian Zoldark. Initiates research on alien technology and starts a war to get the Earth prepared for alien invasion. Where's the mad part in that? He made Valsione for his daughter.
The Medic and The Engineer of Team Fortress 2. The Medic, a GermanDeadly Doctor, is an eloquent, musically inclined follower of Nietzchean Ideals, using his tech to make him and his Team nigh-invincible... all the better for them to dole out the maximum amount of pain and suffering possible. The Engineer is a genial, gentlemanly Texan good ol boy whose normally serene nature masks a burning passion For Science, and a deep seated contempt for and willingness to betray anyone who would dare disrespect him.
Heavy: Doctor, are you sure this will work? Medic: (Evil Laugh) I have no idea!
Thief II: The Metal Age features Father Karras of the Mechanists. He's mentioned in the first game as the fellow responsible for Garrett's replacement ocular, but by the second installment, he's gone completely 'round the bend and is cheerfully intent on bringing about The End of the World as We Know It. Among his achievements are the successful invention of robots, cameras, voice recordings, and motion-sensing automatic cannons in a vaguely Medieval Steam Punk setting, along with horrific cyborgs that constantly weep in agony and beg for death. He also has a preoccupation with Garrett...
Guillaume from Vampire Night. He uses humans for his experiments and even views the vampire hunters as potential test subjects, for crying out loud.
Dr. Kranken from Viewtiful Joe 2 fits the trope (like everything else in the games) to a stereotypical T.
Professor Emma from Wild ARMs 1 has shades of this, most notably when she led the team to a secret underground base that none of your teammates knew anything about, although the team spellcaster is the princess of the town it's built under.
Hanpan: There you go again, with another crazy idea... Isn't this illegal? Jack: Someone stop this crazy professor... Emma: I wasn't sure what I was getting into, so I didn't bother getting a permit.
Xenogears has arguable Big Bad Krelian, for whom everyone on the planet is a test subject, and, on the heroic side, the decidedly eccentric Dr. CitanUzuki. His eccentricity is partially Obfuscating Stupidity, as he's actually a spy. A very intelligent spy.
Xenosaga goes its predecessor one better, giving us an only slightly mad Strangelove Expy in Sellers, the classic obsessive type with pretensions of chessmastery in Dimitri Yuriev, and the tragic and misunderstood type in Joachim Mizrahi. Mizrahi gets extra points for falling to his death while reciting Scripture at the top of his voice.
Tales of Monkey Island features the foppish French (or faux-French) doctor, the Marquis De Singe. (Pronounced by some of the characters like the English word meaning "burn", but "singe" is also French for monkey.) At one point Guybrush asks him why he would build a lightning machine powered by voles and he exclaims, "Science!"
Professor Von Kriplespac (More commonly known simply as "The Professor") from Conkers Bad Fur Day qualifies. He created anti-gravity chocolate and an army of evil teddy bears, and thought that a squirrel would be a good table leg replacement.
One of the main player archetypes in Dwarf Fortress. The kind who builds a 30-storey engine of destruction just so he can have a million streams of magma pouring down onto hapless goblin invaders at once, or constructs a gargantuan bridge just to find out how far you can throw a goblin.
In Monster Lab, the player is an apprentice Mad Scientist.
In the first Borderlands DLC, Dr. Ned is a mad scientist played for laughs.
Dr. Zed might not have a doctorate but he certainly qualifies. A short quest line in the sequel involves him creating two hybrid critters, the Skrakks (Skag/Rakk) and the Spycho (spiderant/Psycho).
Dwarven Paragon Caradin from Dragon Age: Origins was one before his disappearance, although when you finally meet him, he is more of The Atoner than anything else. Likewise, Paragon Branka, whose attempt to recreate the lost art of creating golems by finding the Anvil of the Void led her to abandon her entire family and her lover to a Fate Worse than Death deliberately so that she could get past the traps guarding the Anvil with an endless supply of darkspawn birthed by the Broodmothers her female relatives had become.
In the DLC add-on Warden's Keep, the mage Grey Warden Avernus conducts research into Blood Magic, demonic lore, and the Darkspawn taint, which, while ghastly, has yielded useful results: the Power of Blood talents your character can obtain in the DLC and the means to prolong one's life and halt the Darkspawn taint through Blood Magic. However, if you give him half a chance, Avernus will admit that he made serious mistakes and asks for a chance to undo the damage he caused. He will even quietly accept execution afterwards.
In the AwakeningExpansion Pack, the Architect (a sentient Darkspawn who has freed himself from the call fo the Old Gods and attempted to do the same for the rest of his race, accidentally kicking off the Fifth Blight in the first place) has several elements of this trope.
Also from Morrowind are the lords of Great House Telvanni, a faction of (mostly) Evil Sorcerers. All of them, even the faction's lone Reasonable Authority Figure, conduct experiments which extend their lifespans and enjoy summoning Daedra as guards and test subjects. Even Divayth Fyr's cure for the Corprus Disease fails on every test subject other than the player.
Relmyna from Oblivion expansion Shivering Isles stands out. Obsessed with the power of flesh (no, really), she enjoys creating twisted monstrosities such as Flesh Atronarchs and the Gatekeeper, and considers them her "children". She also conducts some grisly experiments on the concepts of pain and suffering. Oh, and she's on your side.
World of Warcraft has two in its latest expansion, both undead. Grand Apothecary Putress of the Forsaken performs unholy experiments to create a new Plague to destroy both the undead Scourge and all life in general. Professor Putricide of the Scourge tries to do...the same thing, but without the 'destroy the Scourge' part. He also fits the trope better for having a Laboratory of Alchemical Horrors and Fun, as well as being the implied creator of most all of the abominations and similar the players have fought since arguably original World of Warcraft.
The goblin race as a whole fits this, too. Usually their inventions involve Stuff Blowing Up.
Rik'kal the Dissector, a Mantid Paragon, often asks his fellow Paragons to serve as test subjects, and often makes parenthetical asides while giving quests to the player, such as suggesting that the Shek'zeer loyalists' experiments may be dark, but they are not as dark as his, and that only he deserves such power. The other Paragons are wary of him at best.
In Prototype, the Mad Scientist behind the outbreak of the Blacklight virus is Alex Mercer. He wanted to take the original virus and develop it into an even deadlier form. Unfortunately for New York City, he succeeds, brags about his achievement, and then goes and releases it in Penn Station. The player-controlled protagonist character is actually the sentient result, who has assumed Mercer's identity as its Shapeshifter Default Form.
Mass Effect 2s Mordin Solus may qualify, although he's more eccentric than outright mad. He's a Salarian doctor who was formerly a member of a special forces squad, then ran a clinic where he cured a population of a devastating plague while personally shooting attacking mercenaries in the head, both of which he sees as a public service. He also seems to have a taste for Gilbert & Sullivan. He also keeps up a set of ethics and principles that he refuses to break, notably despising the idea of Playing with Syringes and experiments that lead to more suffering than necessary. In the end, he believes in saving lives, even through questionablemeans.
Halfway between them both may fall Tali's father; A Well-Intentioned Extremist with poor judgment and a bit too little foresight, he performs experiments on the geth solely because he believes it will help his people (his daughter in particular). It backfires and he dies because of it.
Henry Lawson. First he creates Designer Babies to continue he legacy and disposes of them whenever they don't meet his standards. And then there's Sanctuary which he advertised as a safe haven during the Reaper War and lured thousands of war refugees and families. Once they got there, they were experimented on and turned into husks and indoctrinated soldiers for Cerberus.
Daniel Dankovski, Bachelor of Medicine from Pathologic is a subversion - he has reputation of one for his revolutionary and unethical hypothesis and experiments(and also due to having personal enemies in academical circles), but he is a genuinely decent and reasonable man, and, as one of the game's protagonists, fearlessly fights The Plague.
The Portal series gives us Aperture Laboratories, a company full of mad scientists. Driven by their grandiosely insane founder and CEO, Cave Johnson, they got started in The Fifties by recruiting the best of the best of humankind and employing them as human lab rats in a vast array of Mad Science experiments. Said experiments involved such things as Body Horror transmutations, irradiation, DNA injections, and their signature teleportation experiments, one result of which was the Handheld Portal Device that forms a core part of the gameplay. Their crowning achievement was Artificial Intelligence, but even here they only succeeded in creating an AI as madly deranged as they were. GLaDOS proceeded to take over the research program... by murdering all the scientists with a deadly neurotoxin. It is then up to the protagonist to enter this maze of insanity and find a way to escape. The closing song to the first game (sung by GLaDOS) makes all this starkly clear.
"Aperture Science: We do what we must because we can. For the good of all of us, except the ones who are dead. But there's no sense crying over every mistake; You just keep on trying till you run out of cake. And the Science gets done, and you make a neat gun, For the people who are still alive."
Portal 2 ups the ante, primarily by sending the player on an exploration of Old Aperture — the test facilities from The Fifties, where prerecorded messages from Cave Johnson lay out the founding principles of the company and its decline into bankruptcy and despair, culminating with the aforementioned push for AI.
Cave Johnson: "For this next test, we're going to have a superconductor turned up to full power and aimed directly at you. No idea what it'll do. I'll be honest, we're just throwing science at the wall here to see what sticks. Best case, you get some superpowers. Worst case, some tumors, which we'll cut out."
More than likely, Cave's overzealous drive to experiment and try anything, even going so far as to fire anyone who questioned the safety of these activities, weeded out any sane scientists and encouraged the eccentric thinking of remaining staff. In the end, Aperture Science was operating off the grid, paranoid of any government oversight, in effect walling themselves in to one giant, death-trap lab.
Daryl, from Harvest Moon: A Wonderful Life. Among other things, he wanders onto your ranch while creepily muttering things, tries to capture a Yeti-like creature in the nearby woods, has a lab that is prone to explosions, spies on your child through the window to observe how children act, tries to steal one of your cows for experiments, and considers taking your DNA to clone you after you die at the end of the game.
Doctor Cranium from Quest for Glory IV is out to reanimate dead tissue and all, but he really doesn't think he's a Mad Scientist. A bit perturbed about the world situation and how he get so little respect, sure, but not mad.
Professor Elvin Gadd of Luigi's Mansion fame also qualifies, albeit he's a benevolent nutcase who seems to channel his eccentricities into his inventions (a machine that turns ghosts into paintings, among other things). It's later learned that he's inadvertantly responsible for all the woes caused in Super Mario Sunshine.
There's also the demented Iggy Koopa, one of Bowser's Koopaling minions. He built the mechs that he and his siblings fought Mario with in Yoshi's Safari. He also has the fits maniacal laughter down pat.
Doesn't stop him from coming back for a rematch, though.
Dr. Odine from Final Fantasy VIII is undeniably brilliant and perhaps the expert on the power of witches in the world. He's the one who actually explains Time Compression to the party. He's also completely amoral - part of why Laguna continues in the position he has is due to needing to keep Odine's research directed towards productive means that won't cause the destruction of humanity.
Lezard Valeth from Valkyrie Profile and it's sequels show Lezard as a mad wizard/alchemist with mad scientist traits. (Though that may be an understatment considering how important to the plot his mad scientist skills seem to be.) He also has one of the creepiest laughs ever to appear in a video game.
In The Sims 2, Mad Scientist is actually the top career rank for the Science career. Also, Loki Beaker from Strangetown is obviously supposed to be one, according to his bio. He also has 0 nice points, which makes him an Evil Genius as well. He and his wife Circe have Nervous Subject in their house and according to the family bio, they are torturing him.
Shin Megami Tensei: Strange Journey has Affably Evil demon lord Mitra. He cordially invites you to share in the bounty of the Schwarzwelt and offers to make you and your comrades citizens of his kingdom-to-come. He also has a tower full of human experiments and is developing insanity-inducing mutagens (which he eventually tests on one of your crew). And his science is... wrong. Very, very wrong. The experiment reports clearly state the demons have really no idea what makes humans tick, so they're cutting as many as they can so they can get a better idea. With all that implies.
Aaaaand we come to Evil Brit Captain Jack. His crew has been fusing demons. So what. The problem is, they're not using the series' traditional Demon Fusion machines - they're using their own. Which mostly involve ripping apart two demons and weave them together.
Gears of War gives us Dr. Adam Fenix. He developed the Hammer of Dawn system, devised the plan to flood the Locust Hollow that required sinking Jacinto, and created the anti-Lambent weapon that appears at the end of Gears 3. He spent more time creating weapons of mass destruction than he did with his family, and he claims that he knew about the impending E-Day but couldn't stop it before it was too late. He tested his anti-Lambent weapon on himself. Unlike many mad scientists, he realized the folly of his work and did everything he could to make up for his failures.
Dr. Ort-Meyer from the Hitman series, responsible for the protagonist's creation. With a reputation as a disgruntled, megalomaniacal geneticist (even pulling an extensive They Called Me Mad! speech in the first game's finale), he was capable of creating a mindlessly loyal and equally lethal version of 47 over the course of the game, which nonetheless ended up being destroyed by 47 (although there survived a more primitive version which went on to serve as a minor antagonist in Silent Assassin). The backstory of Blood Money deals with the impact of his creation's legacy and the prospect of it falling into the wrong hands.
Dr. Paul and Dr. Miranda from Escape From St Marys disguise their time machine as a coffin so that it's "inconspicuous." Their invention threatens to destroy the universe; they seem mostly unmoved by this.
Seath the Scaleless from Dark Souls is a dragon that combines this with Evil Sorceror. He is described as the grandfather of sorcery and the creator of various magical creatures like the Moonlight Butterfly. He went insane trying to decipher the one mystery that eluded him his whole life: why he was the only dragon born without the scales of immortality that every other dragon had.
Dr. Mundo performed sadistic experiments on anyone he could catch until he was run out of town. Lacking subjects, he experimented on himself, transforming into a drooling brute with immense strength, regenerative powers, and Hulk Speak.
Singed was Warwick's student, but when he created his greatest invention he decided to name it after his patron. Hence the Insanity Potion. In addition to the chemicals he throws around, his personal enhancements have made him immensely strong and durable.
Viktor turned himself into a cyborg, and wants everyone else to undergo a similar transformation. Fortunately thus far his method has been to prove how superior his enhancements make him instead of doing unwilling conversions.
Ziggs is obsessed with explosives and extremely reckless with them. After saving the Yordle Academy that expelled him for his dangerous methods they admitted him in gratitude and recognition of his skill, then directed him to the League. An honor, certainly, but one that ensures he spends a lot of time away from them.
Vel'Koz is an Eldritch Abomination from the Void who is not as much malevolent as curious, eager to study the new world he has entered, particularly the life forms residing in it. Also he studies things by disintegrating them.
The Pokémon games usually have a few scientists willingly working for the main villains.
Dr. Malcolm Betruger from Doom 3. In the expansion pack Resurrection of Evil, he becomes the Maledict.
Reality On The Norm: The recurring character Dr. Die Vie Ess, who fills every evil scientist cliche, complete with a mansion and a basement with a big vat of acid, as well as having his eyes go crazy when he talks.
Mana Khemia gives us Jess, a Rose-HairedGenki Girl who loves to experiment with alchemical bombs and medicines. And by "medicines", we mean "potions that magnify cavity pain and/or turn people green." The fact that her experiments tend to blow up in her face might actually be a good thing.
Dr. Elliot Sinclair, Big Bad of The Journeyman Project, and inventor of the Pegasus time machine, which jumpstarted the foundation of the Temporal Security Agency.
Dr. F of My Sims Kingdom, who enthused after a successful experiment that "History will replace the word 'science' with the name 'F'!"
There's a whole faction of them in Pandora First Contact, though they tend to be good, honest, and upright, they are sometimes too enthusiastic in their search for the truth at the expense of many lab monkeys' brains.
The chronologically final installment of The Tale of ALLTYNEX trilogy, Kamui, has the Big Bad Xaffiquel become this after his daughter Panafill de Alice was uploaded into one of the titular Kamui fighters.
In Robopon, Dr. Zero is this in both games. The sequel reveals it runs in the family with his brother, Zeke, and his father, Dr. Zero, Sr.
More of an engineer/designer, given the setting's Magitek, the title applies to Kang the Mad of Jade Empire. It's in his NAME, after all.