It would also be cool if there was something integrated in the game like IWS to give the game more difficulty, or something along the lines of realistic damage that can be turned on or off.

I think it would be pretty cool if they didn't make groups as black and white as bethesda has been doing recently specifically with the Thalmor of Skyrim, Caesar's Legion of F:NV, and and Enclave of nearly every fallout game save for F:NV. The idea of a group based around discipline, reliability, and rigid structure with tribal roots sounded really cool...but how evil they made Caesar's Legion was just ridiculous. I am a huge fan of making tough choices and having games that allow for people to choose sides in a conflict, but I would like it to be more difficult then crazy slavers and the republic trying to protect everyone.

Also a bigger focus on plot. I loved the variety of things you can do in F:NV but the stories/quests were very bland. I love FO:3 just because of the main quest. I want a long spanning quest that is a bit more gripping...or at least something more then "you got amnesia, now decide the fate of New vegas"

More npc, more gigs of ram to handle mods ... and absolutely NO MULTIPLAYER