Well, Dragon Age at least will have its own non-DnD fantasy world and rules system, so that's something different. I hope it's different enough to be interesting, and not just a slight tweak to avoid paying DnD royalty fees. One reason I like the Witcher is the way it has its own distinct flavor of fantasy world. It borrows heavily from the classic genres (they all do), but it had a different enough twist to be interesting.

It would also be nice to see more sci-fi themed RPG's that aren't just shooters wrapped inside a lightweight RPG framework like Mass Effect, or Bioshock. I'm not sure if the upcoming Fallout 3 qualifies. I didn't play the earlier games in the series.