|Picture from ign article|
I point out some of them I find interesting and what I could use. Descriptions from picked villains and their usages are short, as they are described in ign.com article already. These are just small ideas I have from them in what game you could use them. There might be better games I suggest here, or you could possibly modify these villains to any genre making them a bit different (for example sniper Wolf from MGS could work in fantasy setting as well etc.)
So, here are few I find worth mentioning. It doesn't mean, that others are not good to use. Look at the list, take idea seeds for your rpg campaign villain. And if you get ideas how to use these villains listed in a campaign or game setting, feel free to post in in comments. I appreciate your ideas and will read them with great interest!
http://www.ign.com/videogame-villains/98.html Gary Oak from Pokémon series. Annoying person, who is always ahead of main character. In roleplaying game he could be in a campaign this person who is not your enemy, but you start to hate. In the other hand, it could ruin the fun for the players if there is this NPC who always is a bit better, and always a step ahead. So be careful when making this kind of antagonist.
http://www.ign.com/videogame-villains/97.html Shang Tsung from Mortal Kombat. In final battle the main villain can change himself to represent player character's skills. With one on one battle this can be really challenging and interesting because character has to basically fight himself. If there is adventurer party, it is not that big of a challenge as there are many against one character replica. Still, it could be powerful but emulate in top of that one character's skills in addition for his own powers.
http://www.ign.com/videogame-villains/96.html Adrian Ripburger from Full Throttle. Big company chief works with almost any rpg. Could be good in Cyberpunk where he controls street gang.
http://www.ign.com/videogame-villains/92.html Sniper Wolf from Metal Gear Solid. The whole scene with Sniper Wolf from MGS game could be good drama and action for roleplaying game. What will be character's decision in that situation?
http://www.ign.com/videogame-villains/90.html Dagoth Ur from Morrowind. Players have to save the world from evil god who causes all bad things all around? And is basically immortal? Dagoth Ur will be great meta-plot and epic and hard final antagonist.
http://www.ign.com/videogame-villains/87.html Officer Tenpenny from GTA: San Andreas. Bad cop in modern setting. He has law behind him and killing an officer is never a good thing. But he is bad cop and characters get into trouble with him and soon after characters aren't that bad anymore when there's corrupted law in the other half.
http://www.ign.com/videogame-villains/85.html Sub-Zero from Mortal Kombat. Exalted could be good for Sub-Zero, or grim and dirty superheroes game.
http://www.ign.com/videogame-villains/83.html Death Adder from Golden Axe. Conan rpg could use this kind of bad guy, or some other low magic fantasy setting.
http://www.ign.com/videogame-villains/80.html Bydo from R-Type. The whole background of the bydo is really cool, and can be put in science fiction game.
http://www.ign.com/videogame-villains/79.html Jafar/Vizier from Prince of Persia. Evil ruler what gives characters a plot. To save a princess or otherwise she's dead.
http://www.ign.com/videogame-villains/77.html Shadow Link from Zelda. Character's evil shadow twin? There'd dobbelgangers in fantasy games, but if it was more personal. In Kult if you mess up your mind bad enough, your soul will manifest it's physical shadow half.
http://www.ign.com/videogame-villains/75.html Lavos from Chrono Trigger. I see some Mythos like plot here. Ancient god monster who will bring apocalypse. That is time for player characters to act.
http://www.ign.com/videogame-villains/74.html Diablo from Diablo. What would be better final villain monster in D&D dungeon to hell than devil demon himself?
http://www.ign.com/videogame-villains/73.html Alma from F.E.A.R. Make your shooting action game into horror with Alma. While having fun throwing dice and shooting enemy troops, you have horror aspect and also mystery in background to solve. Test Code/X from Burger Games for great rules to run F.E.A.R. action.
http://www.ign.com/videogame-villains/71.html Dark Falz from Phantasy Star. Can be great plot for Fading Suns. Is Dark Falz some unknown creature, or part of symbiots? What ever it is, it might be behind the fading suns phenomenom.
http://www.ign.com/videogame-villains/69.html Cyberdemon from Doom. Well, Doom itself is great setting for futuristic dungeon crawl, and cyberdemon would be great villain to characters to deal with... firepower.
http://www.ign.com/videogame-villains/68.html Calypso from Twisted Metal. For post apocalyptic rpg (I suggest Taiga here) Calypso would be great bad gang leader with background. And with post apocalyptic I mean Mad Max.
http://www.ign.com/videogame-villains/67.html Goro from Mortal Kombat. I haven't played Exalted, but I so see Goro being there.
http://www.ign.com/videogame-villains/65.html Dr. Nefarious from Ratchet And Clank. Humorous cartoon styled superhero game here's your villain.
http://www.ign.com/videogame-villains/61.html Predator from Aliens Vs. Predator. Predator are awesome, and human troopers easy hunt. There's great fan made supplements for Savage Worlds with predator as a monster. Kill it before you are killed. Predator works in modern today settings to science fiction, and why not in even fantasy.
http://www.ign.com/videogame-villains/60.html Prophet of Truth from Halo. Yet again science fiction antagonist to deal with.
http://www.ign.com/videogame-villains/59.html Nemesis from Resident Evil. Want a big bad zombie for your All Flesh Must Be Eaten? Nemesis is one choice to wet your player character's pants.
http://www.ign.com/videogame-villains/57.html Origami Killer from Heavy Rain. Hunters have something to hunt as this is a great Slasher (Hunter: the Vigil + Slasher sourcebook).
http://www.ign.com/videogame-villains/55.html Ares from God of War. For your Greek OSR rpg (cannot remember the name) great villain with a plot.
http://www.ign.com/videogame-villains/51.html Tank from L4D. Also great surprise for AFMBE characters to encounter. It first eats your bullets, then eats you.
http://www.ign.com/videogame-villains/47.html SHODAN from System Shock. Trapped in space ship where everything goes wrong? Great campaign for science fiction horror trapped in a spaceship and trying to both survive and figure out what is going on.
http://www.ign.com/videogame-villains/46.html Grue from Zork. Make your Call of Cthulhu characters be a bit more afraid of dark.
http://www.ign.com/videogame-villains/45.html Flood from Halo. Make your AFMBE a science fiction setting, or make Fading Suns symbiats more twisted.
http://www.ign.com/videogame-villains/41.html Arthas from Warcraft. This bad guy's whole background story will make an awesome Dungeons & Dragons campaign altogether.
http://www.ign.com/videogame-villains/39.html Harbinger from Mass Effect. What could be more dangerous than a villain you don't confront, but you confront his minions what this villain gives power to?
http://www.ign.com/videogame-villains/37.html Lich King from World of Warcraft. If your campaign with Arthas was not enough, give more experienced characters sequel to your campaign with Lich King.
http://www.ign.com/videogame-villains/35.html John Henry Eden from Fallout. Was there some hope in your post apocalyptic game? Ruin it introducing new American president.
http://www.ign.com/videogame-villains/34.html Kain from Legacy of Kain. For Vampire: Dark Ages Kain could be really powerful ancient vampire, who was betrayed and now seeks revenge. He might be antagonist, or even powerful ally or leader for characters.
http://www.ign.com/videogame-villains/33.html Darth Malak from Star Wars: Knights of the Old Republic. Obviously for Star Wars games the main thread in whole campaign. With little modification could also be evil wizard in fantasy settings. Or even in Vampire, if you change fighting ships to ghouls and shovel heads.
http://www.ign.com/videogame-villains/30.html Ultros from Final Fantasy. What if characters encountered a talking carnivorous purple octopus what wanted to kill them in Dungeons & Dragons. In different campaigns. Several times. Go find out.
http://www.ign.com/videogame-villains/27.html Dr. Breen from Half-Life. In future if characters are on guerilla's side, Dr. Breen could be the enemy they fight against.
http://www.ign.com/videogame-villains/14.html Albert Wesker from Resident Evil. What would a zombie game be without a megalomaniac psychopath, who tries to get advace from the situation? Make a bad guy in your AFMBE campaign... zombies are not your only trouble after it.
http://www.ign.com/videogame-villains/8.html Psycho Mantis from Metal Gear Solid. Somehow I see Nosferatu possibility here for Vampire.
Almost any villain from that list could be a good antagonist for a campaign with next to no modification, some could be modified or obvious ones could be put in totally different genre to create something new.