In Double Dragon, Jimmy Lee went from being an ally to his brother Billy in his battle against the Black Warriors, to being the true leader of the gang in the NES version due to the removal of the co-op mode. Whereas the arcade version only has the battle between the Lee brothers occur if two players clear the game together, the NES version simply has Jimmy show up to fight his brother after Willy (the arcade version's final boss) is defeated. Strangely, the NES versions of both sequels feature Jimmy as a player character once again, ignoring his role as a bad guy in the first NES game.
A lesser known example comes in the form of the Mission 4 boss in the NES version of Double Dragon III. He resembles one of the Urquidez brothers from the arcade version of the game (specifically Sunny), who were playable characters in that version of the game, but unlike Chin and Ranzou, he never becomes part of the Lee brothers' party after being defeated.
Despite being a hero and even a member of The Avengers, Echo is portrayed as an unambiguous villain in the Daredevil video game adaptation.
While he's not exactly "good", Scorpion from Mortal Kombat tends to be portrayed as a straightforward villain in most of his adaptations, often working for the main bad guys.
Anna Williams of the Tekken series suffers from this. While she's certainly not heroic in the source material, she is shown multiple times to be nicer and somewhat more compassionate than her cold-blooded sister, Nina. In every animated feature and spinoff game, though, the dynamic is totally reversed, making Nina the more sympathetic Anti-Hero and turning Anna into the evil one.
While Smithers has never been a truly sympathetic character on The Simpsons, he never went so far as to rob a jewelry store and kidnap Maggie like he did in the Konami arcade game.
Darkrai is portrayed as a Dark Is Not Evil Pokemon in the Pokémon games, hiding itself away voluntarily to try and prevent its power to trap other creatures in nightmares from afflicting others, even making sure that its counterpart Cresselia is close by to treat anyone affected. In the Mystery Dungeon series, it is a much more malicious character who plots to plunge the world into eternal darkness For the Evulz. However, this Darkrai eventually loses its memory and can be recruited postgame.
The video game adaption of the Fighting Fantasy gamebook Deathtrap Dungeon has this with Baron Sukumvit. The original wasn't exactly a saint, but was portrayed more as an opportunistic noble and a fair ruler, while the video game version has him as the Big Bad, and a tyrant, and has more in common with his villainous brother Lord Cairn from the sequel book Trial Of Champions.
Axonn in BIONICLE Heroes appears as a brute henchman for the Piraka and is the boss of his level. In the official story, he is actually the mightiest helper of the main characters on the island of Voya Nui, and periodically wipes the floor with the Piraka. Then again, the game threw out practically all of the canon elements in exchange for a better gameplay.
Iron Will in Adventure Ponies. In the show, Iron Will could be intimidating, but the most "villainous" thing he did was rudely demand that Fluttershy pay him for his services, and he eventually accepted that she wasn't 100% satisifed. Here, he's a level boss.
The Fugitoid, a robot with the brain of human scientist, has always been portrayed as an ally of the Turtles, with the sole exception of Teenage Mutant Ninja Turtles The Manhattan Project where he is instead treated as a recurring minion in the sixth and eighth levels.
In the comics Hybrid was an almost completely heroic character; in the game, he is an entirely villainous boss. His "sibling" Scream also tries to attack a daycare, while in the comics (where she eventually pulled a Heel–Face Turn) she once expressed disgust at the prospect of another villain killing and eating children.
Ronan the Accuser started out as a standard cosmic villain, but was always presented as loyal to his own people's justice system and possessing of honor, and when Marvel Cosmic was highlighted after Annihilation, he was presented as a hero, which became his default characterization in every book since. In-game, Ronan is a two-dimensional, genocidal maniac like in the movie.
Yondu Udonta, who was a member of the Guardians of the Galaxy in the comics and a superhero. Even in the movies, which the game heavily borrows from, Yondu is mostly faking his antagonism to look strong in front of his crew and is proud of Star-Lord, who he sees as something of an adopted son. In the game, however, he's genuine in his desire to kill Quill and is angry instead of amused that Peter swapped out the Infinity Stone he was trying to steal for a troll doll.
In American McGee's Alice, several characters from the works of Lewis Carroll get this treatment, including Tweedledee, Tweedledum, the Queen of Hearts, the Dormouse, the March Hare, and the Mad Hatter. However, the Mad Hatter does have a Heel–Face Turn in the sequel and becomes one of Alice's allies.
Harvey Dent is an unusual case in the DS version of Lego Batman: The Video Game. While he became the villain Two-Face in all continuities, he was originally an honest district attorney. While playable as both, he is marked as a villain as Two-Face and pre-scarring Harvey.
In the GBA version of Scooby-Doo and the Cyber Chase, the culprit is a random character, not necessarily Bill as it was in the movie. This is presumably to keep people who saw the movie from getting it right based on that alone.
In the Game Boy version of The Jungle Book, Kaa gets this treatment as he did in the film, but Baloo, an ally to Mowgli in both the film and the book, is also fought as a level boss.
In the PSP version of The Sims 2, Vidcund Curious kidnaps Pascal's child, Tycho, for money and research. And he's the one who's supposed to be abducted by aliens in the PC version...
You know those singing squeaky slugs from Flushed Away? They are, for some reason, out to harm the main characters in most of the video game adaptions despite not showing any hostility towards the main characters in the movie at all.
In at least one Astérix video game, Cacofonix is fought as a boss. In the comics themselves, while he is a nuisance and a Giftedly Bad musician, he is an ally of the main characters and not at all a villain.
In the comics, most of Anarky's actions were targeted at specific individuals, and although some of his actions put his targets in critical condition, he wasn't a killer and he would avoid collateral damage. In Batman: Arkham Origins, Anarky plans to blow up buildings connected to what he believes are the root problems of society, and he's unconcerned with who might get hurt in the process. He's also portrayed as somewhat less rational than his comic book counterpart. You probably wouldn't hear the comic Anarky ranting against soft drinks, for example.
In Batman: The Animated Series, Ferris Boyle, the guy who turned Victor Fries into Mr. Freeze was a greedy jerk who didn't care if he ended a life just to save money, and him turning Victor into Freeze was a reaction to Victor pulling a gun on him. In "Cold, Cold, Heart" DLC, he asked Victor to build cold based weapons in exchange for helping his wife, only to renege on the deal. Later he was willing to kill Batman and Freeze so he could leave no witnesses, and was preparing to kill Nora in front of Freeze out of spite.
Calendar Man. In the comics, he was a petty criminal whose holiday-themed crimes rarely involved murder. In the Arkham series, he's portrayed as a sadistic Serial Killer who crimes revolve solely around murder.
Batman: Arkham Knight does this to Jason Todd. As the titular Arkham Knight, he's party to a chemical attack on a major metropolitan city, something that, even at his worst, his comic counterpart hasn't done.
The Scarecrow himself, while very much a villain, occasionally has sympathetic moments in the comics, generally relating to his backstory as a bully victim and severe abuse from his family (great-grandmother pre-Crisis, father in the New 52). In the game, he lacks any sympathetic qualities and is even more monstrous than his comics incarnation, easily one of the most vile characters in the series. Background material suggests that this version of Jonathan Crane isn't even mentally ill, just pure evil.
Much like in Batman Returns, the Penguin was shown to be quite psychotic, sadistic, and brutal. This version lacks the Affably Evil and Wicked Cultured traits of the comics' gentleman of crime, and has displayed racism, misogyny, homophobia, and abelism.
While most incarnations of the Riddler are fairly narcissistic, they are, at the least, humble enough to respect Batman as a Worthy Opponent and are on good terms with the rest of Gotham's villains. Arkham's Riddler, by contrast, is a smug, egotistic, patronizing, arrogant, and thoroughly obnoxious Jerkass who is either ignored or outright belittled by Batman and some of the other villains.
While Jack Ryder could be a jackass, it was usally as part of a feint for his actions as The Creeper. Here, he's a legitimately self-serving and egoistical asshole.
Sonic Boom: While never exactly a saint, Shadow was generally depicted as a Noble Demon and a Pragmatic Hero in the mainstream video games. Here, he's an arrogant, abrasive Jerkass who openly mocks Sonic for relying on and trusting his friends.
Done in-universe in Borderlands2. In the main game, the Guardian Angel was a tragic but ultimately heroic character who sacrifices herself to help stop her father, Handsome Jack. However, the Tiny Tina's Assault on Dragon Keep DLC -where the heroes play a setting-appropriate Dungeons & Dragons-style game run by Tiny Tina- features a blatant expy of her that tricks the heroes into releasing it and then turns into a spider-demon and tries to kill them. Lampshaded by Lilith, who tries to explain that the Guardian Angel wasn't really evil, but Tiny Tina refuses to listen because she blames Angel for Roland's death.
In Die Reise Ins All we met Sherlock Holmes. First he seems to be exact to the character as he is known from the books. Later it's revealed that there was no Sherlock Holmes all along. It was Moriarty in disguise from the beginning.
In Yu-Gi-Oh! Forbidden Memories, Priest Seto rivals Death-T era Kaiba in terms of villainy and pettiness, as the manga arc where he first appeared wasn't even close to being completed when the game was released. Among other things, he served as Heishin's right-hand man and was responsible for seizing all of Egypt, kidnapped Teana as a hostage to lure you into a deadly Shadow Game, was fine with the murders of the Prince's parents and enacted Heishin's order to seal the tombs, preventing the Prince from seeing his parents' bodies, and was descended from evil sorcerers and plans to renew a pact with DarkNite in order to rule the world. His stated reason for doing all this? He's of noble blood and you're not, therefore he deserves to rule.
In Equestria Bound, while a lot of the are jerks in the show, much like Giygas in the original game, Nightmare Moon is able to influence beings from the past to do her bidding, all of whom have a grudge against Equestria or the mane caste for some reason. Some examples being Trixie and Gilda, both of whom later pulled a Heel–Face Turn in the show.
Darkstalkers: BB Hood is a darker incarnation of the famous Little Red Riding Hood. Instead of being the innocent girl who had a terrible run in with a big bad wolf, BB Hood is an Ax-Crazy, sadisticPsycho for Hire trying to hunt down and kill every darkstalker, even if they are good and haven't done anything wrong. In fact, most of her victory quotes are taunts to her now dead opponents.
She's even considered evil enough that she appears in Project X Zone 2 as an enemy.
Hotline Miami 2: Wrong Number features an in-universe example with the movie about Jacket's exploits from the previous game. While in the first game he rescued a hooker from the Mafiya and she came to live with him and serve as his Morality Pet and his only hold on sanity, in the movie Jacket's Expy the Pig Butcher rapes and abducts the hooker from several teenagers, who eventually flees and calls the police on him. Once he ends up in the police interrogation room he breaks out and slaughters his way to her, only for her to shoot him dead as soon as he steps through the door.
In Taz Wanted, the Big Bad is revealed to be none other than Tweety Bird, a well-known heroic character among the Looney Tunes. In the game, he's attempting to kill Taz, take his country Tasmania over, and construct an amusement park over it to gain profit.
Clyde is usually a recurring friendly character who's fully onboard with the boys and their ideas. However, in the game he becomes an Arc Villain who's screwed over his classmates in order to harness the power of the Stick of Truth for himself.
In The Wolf Among Us, the Huntsman who saved Little Red Riding Hood from The Big Bad Wolf has become an unpleasant jerkass. He actually reveals that he never intended to become the hero we all knew from the famous Fairy Tale. In fact, he broke into the Grandmother's house because he wanted to rob her, but by coincidence the Wolf just happened to be there simultaneously and he attacked him in self-defense. Unaware of his true intentions, the Fables praised him as a hero, which he fully embraced in order to hide his true character. Fortunately, he Took a Level in Kindness after the big bad wolf, of all characters, talks some sense into him.
The Crooked Man as well. In his original fairy tale, the Crooked Man is just some random guy living his everyday life despite literally being in a crooked shape. In the game, he's the Big Bad.
In Scribblenauts Unmasked, Anti-Villains such as Catwoman are relegated to this role for the sake of simplicity. More or less, if they attack civilians in any way, no matter how noble they are, they're considered villains outright.
In Killer Instinct, Ben Ferris was originally conceived as a small-time arsonist who was transformed into a constantly burning man by the twisted experiments of UltraTech's chemical weapons research division. Entered into the tournament under the codename "Cinder" with the promise of his freedom as a reward for winning, Ben instead was so horrified by what he had become that he actually sought someone to kill him, and canonically, Glacius was the one who granted him his wish. In the 2013 reboot, Ben is a much less sympathetic figure: a Sociopathic Soldier turned thief-for-hire who infiltrated UltraTech's research division only to be caught by ARIA, and in turn offer his services to her. This version of Ben Ferris willingly accepted being transformed into Cinder because he loved the idea of having the fire powers, and his personality is basically if the Human Torch were also a completely psychotic Blood Knight.
Supplementy materials show the alternate universe Wonder Woman was already veering into She Who Fights Monsters territory even before assisting the alternate Superman in taking over the world. In the game proper, she's a Blood Knight, something which horrifies the mainstream Wonder Woman.
The alternate Sinestro is also a good deal eviler than his mainstream counterpart, and with Wondy functions as a devilish voice in Superman's ear to push him further past the Moral Event Horizon. Perhaps most strikingly, his viewing of the Earth Lanterns as Worthy Opponents is completely omitted from this version; he gruesomely kills both Kyle and John personally, then manipulates Hal into murdering Guy.