In Double Dragon, Jimmy Lee went from being the Player 2 character in the arcade version, helping his brother Billy defeat 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 both players completed the game together, the NES version simply has Jimmy show up to fight his brother after Machine Gun Willy (the arcade version's final boss) is defeated. Strangely, the NES versions of both sequels feature Jimmy as Player 2 once again and don't even acknowledge 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 wasnt 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 and Gilda 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. Likewise, while Gilda was a rude and insensitive Jerk Ass, she never got violent. Here, they're level bosses.
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.
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 suppose 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.
Jumba is one of the Disney villains in the Kingdom Hearts series, albeit a relatively ineffectual one. While originally a villain in Lilo & Stitch, he made a Heel-Face Turn and became one of Lilo's friends for the rest of the series. The same goes for Sparky, portrayed as an violent monster in the game but who also pulled a fairly early Heel-Face Turn.