Stupid topic, IMO. Why limit yourself to just games that don't have sequels? Most of my favorite games like Burnout 3, Bioshock, Mass Effect 2, Prince of Persia: SoT, Half-life 1 + 2, Dead Space 2, inFAMOUS, God of War, Red Faction, etc have or are sequels (regardless of gen). If a game is good, isn't it pretty much guaranteed to have a sequel?
If I had to pick a standalone game, I'd say either Enslaved, Alan Wake (is getting a XBLA sequel), Metro 2033 (sequel soon), Batman : AA (sequel soon), Prince of Persia 2008 (shut up, it doesn't have a sequel and is unrelated to rest of series), Mirror's Edge (probably be a sequel sometime), SoTC (I doubt it counts as this gen)... Darksiders? Oh wait, that's getting a sequel.
You see how hard and pointless this is?!