you're going to get so many different answers that it isn't going to do you any good. Oblivion, Bioshock, Condemned 1 & 2, Ninja Gaiden 2, Orange Box. but that's just my list. everyone has different tastes. you're best bet. do some research since you are on a gaming site.
If you want a FPS: Bioshock If you want and RPG: Oblivion... I couldn't get into Mass Effect myself... I didn't try very hard though. But it seemed like the Sci Fi RPG worth trying.
I have a hard time getting into ME mainly because it seems like I'm just learning new names for every sci-fi cliche imaginable... with a cover system. To each their own though.
I agree with a lot of the recommendations you see above... RPG wise, you should get one depending on your taste. Oblivion if you like medieval, Eternal Sonata if you like JRPGs, or Mass Effect if you like Sci-Fi. Shooter wise, Bioshock is probably your most solid single player bet. The Orange Box isn't bad either, because you get a lot of content, but I feel that the multi-player is a big part of that game. If you are more into racing games, check out Burnout Paradise... There's a ton of single player content.
Condemned Criminal Origins + Bloodshot, Ninja Gaiden 2, Mass Effect, BioShock, the relatively-inferior-but-still-awesome 4/5ths of the Orange Box, Oblivion, Assassin's Creed, Grand Theft Auto 4, Crackdown, Dead Rising, Rainbow Six Vegas, Soul Calibur 4, Dead Or Alive 4, FEAR, Ghost Recon Advanced Warfighter + 2, - all these games have great campaigns.
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