Spore

Spore is an excellent game! So far I've just hit the space age, but this game has been...
Asteroids
FPS
RPG
RTS

Its got the huge range of customisability of Sims (same guy), but without any of that family stuff ;-D
I spose the only thing holding it back so far is the slightly dated cartoony graphics, but I'm not sure you could get away with making it any more serious.