I would say Washington State. It would be very interesting to see a large portion of the state to be fully rendered. What's really interesting would be the drastic change of environment. Potential DLC? After all, Washington State is a forest environment with a medium sized city about the same size as D.C with the Space Needle which could function as the main "landmark" for this game. Not to mention if you get tired of the forest environment and wish to go back to the wasteland desert, just go over the Cascade Range. The east side of Washington is a desert like farmland much like Fallout 3's environment outside the D.C downtown area.
This also allows so many DLCs. Such as venturing far west to see the Pacific Ocean and the Puget Sound area or venturing far east and seeing the Wasteland desert. Not to mention it's nice to see a change. After all, Washington gets quite a bit of rain and because of the nukes, it would also be a very cold and snowy environment. Here's a bit of concept art for Seattle, the "Vegas Strip" of Washington.
http://images1.wikia.nocookie.net/__cb20091113193350/fallout/images/a/a3/V13_Snow_City.jpg
Heck, it can even span down south into Portland Oregon.
Enemies would be mostly people but animals would still exist. Mutant bears, a snowy type of Deathclaw, large hairy wolves, heck even Mirelurks could exist if the game takes place near the Pacific Ocean.