Play as the villain... Because it's fun yo.

City of Villans was probably the only game where you were literally a on the bad side.

Isn't just about every Grand Theft Auto a villan simulator? You're running around stealing cars, blowing shit up.
Aside from that, Bioware games are another possible choice.

Portal and Portal 2, you play as a horrible person who only seeks to ruin the life of a saintly AI who only wishes to test.

Overlord

ol' Lucasarts Tie Fighter

Any game with a morality system lets you play as the bad guy, to an extent. But there really aren't that many modern games where you are really the villain. I love being evil in video games. Its so liberating. But I suppose it would be hard to keep most people motivated in a game where you're the villain trying to do bad things. You have to make it kind of tongue-in-cheek, like Overlord or Dungeon Keeper.

Stubbs the Zombie in Rebel Without a Pulse - don't go killing zombies, be the zombie yourself and turn the whole world into likes of you. Also it's like a 50's comedy movie, with a great soundtrack.

Fable - The Lost Chapters.

company of heroes opposing fronts and tales of valor:

the main game you can play as werhrmacht in multiplayer, in the expansions you got a campaing dedicated to the panzer elite, and small nazi squadrons.

men of war

same, you get a full campaing dedicated to the nazis, as well as some bonus missions.

Plague Inc.: Evolved cool game =)

Fallout

Star Wars: The Old Republic (you can be a sith, so badass), or DC Universe Online

Evil Simulator ?

Fallout 3 or Fallout NV? Also Star Wars Force Unleashed games.

evil genius.

Dominions 3 playing as Late Ermor if you want to black out the sun and conque the world with armies of skeletons and zombies...

In medieval total war 2 warhammer mod you can play as skeletons too.

What about playing germany in some ww2 game like hearts of iron, japan in war in the pacific admiral edition, the US in squad battles vietnam, the UK in ageod pride of nations... not the same thing but but if you know your history...

But most of all dwarf fortress ? What about running a fortress of necromancer vampire evil dwarves sucking blood out of captured goblins and elves ?

Mafia 2...

In Crusader Kings you can play as a villain. It's pretty much a murder simulator.

Tropico games, quite obvious.

Also Unholy Heights, where you play as the devil. You're the landlord of a bunch of apartments and you have to lure adventurers to your building and then horribly murder them with your minions, who are also your tenants.

The Dungeon Keeper series, Overlord, Final Fantasy: My Life as a Dark Lord, technically Final Fantasy Tactics Advance, Destroy All Humans, Prinny: Can I Really Be The Hero?. You could make the argument that you remain a bad guy in Pokemon XD as you keep stealing and keeping Pokemon.

There's a bunch of freeware and flash games that let you be the villain, but I can't name any off the top of my head right now.

Aliens Vs Predator games, no one is really nice in there but it's epic :P Predator on PS2 too was awesome. GTA, SR, Postal, Kane and Lynch, Blood 1 and 2 ...