I think that Spore should have been able to be that type of game, but it miserably failed, and that is sad to be honest, I was really looking forward to play it for many years. I have to agree with Fallout 3, while I myself am not very interested in it I can at least see that it has a lot of potential especially for the modding community, it really looks like Oblivion set in a post-apocalyptic environment, and that isn't a bad thing at all, I will certainly be curious to see how it fares over time.
Then of course the inevitable StarCraft 2, I know I won't buy it, but it doesn't take a rocket scientist to know that it will sell big time, it has in my opinion the potential to be the most selling PC game of all time, and the only other game with that type of attraction is Diablo III, I can see 2009 and maybe 2010 being the Blizzard years. I for one will prepare myself to lose (yes, lose, certainly not investing it) around four to five years of my social life to play it (outside of my job time, of course).
For me it's all about Diablo III and Empire: Total War... and maybe, I just say maybe FarCry 2 IF... I say IF the modding community is flourishing enough for it to prosper in different ways for years to come similarly to Oblivion for instance.