Mass Effect has kind of an old-school sci-fi setting. It plays a bit like a shooter.
Knights of the Old Republic 1 and 2 are Star Wars. Actually, they're really, really Star Wars -- many people said that KOTOR felt more like what they think of as Star Wars than the prequels did.
Jade Empire draws on Asian (mainly Chinese but not entirely) themes for its setting and inspiration. It's like kung-fu fantasy.
Arcanum: Of Steamworks and Magick Obscura is all, like, magic-steampunky. So elves and magic but also guns and mechanical stuff. I've never played this one myself.
Vampire the Masquerade: Bloodlines is set in modern times. It's kind of a "dark fantasy" thing, i.e. lots of horror elements but the story structure itself isn't horror.
Planescape: Torment has one of the most interesting fantasy settings ever, and, in my opinion, the best RPG storyline hands-down. It's rather old now, but if you can tolerate Fallout 2's graphics and interface you'll have no problem with Torment. Go play Torment now!
The Deus Ex games and BioShock are mainly shooters but have RPG-ish elements in them.
-- Alex