Somewhat late to the E3 tide, the BethBlog and Fallout twitters point to a preview on GameSpy's affiliate Fallout 3 site, Planet Fallout, based on hands-on time at E3.
After playing the press demo at E3 for nearly an hour, I can safely say that I walked away with the full intent to pre-order the collector's edition. Of course, I might be considered a bit of a fanboy since I work for Planet Fallout and all, but hear me out before completely dismissing my opinions.
If you enjoyed the art direction of Fallout 3, you're going to find a similar but different approach taken to the desert atmosphere. From my limited experience, it wasn't as dreary and depressing at all times but there were certainly moments where it felt that way; it just wasn't as pervasive.
Don't think for a moment that Obsidian got off easy and was able to port over a lot of the Fallout 3 rendered objects either. The developer standing next to me remarked that one of the few things that actually were able to be directly drawn from Fallout 3 was some of the roadways. Other than that, everything was either manipulated from stock versions or created from scratch.