I am not saying Bethesda should include any of these, this is just stuff I think would be fun to include. Feel free to include your own ideas.
First, I think they should take a few pages from The Elder Scrolls, and give you the option of playing as either a regular human, a ghoul, nightkin, or regular super-mutant. Humans can be further divided into the subclasses of Tribal, Vault Dweller, NCR Citizen (or some other post apocalyptic civilization). Each character background will be given its own set of bonuses and weaknesses. There should be no bonuses or penalties for race, or gender though, since that gets into dangerous territory.
Your character should be allowed to marry. It should mimic marriage in the Skyrim universe in function.
Your character should be able to retain sixual orientation perks, such as Confirmed Bachelor, Ladies Man, Black Widow, ext because six brings a whole new level of immersion to the game. The game should continue to cut away from actual six scenes, in order to avoid controversy.
There should be an option to tone down the gore for younger players. I love watching guys blow apart, but as a single father, raising a small boy fulltime, I am uncomfortable playing my favorite games (Fallout New Vegas and Skyrim) around my son.
multiplayer or online isn't that big of a deal for me, because I like the go it alone aspect of these games. There are other games I play when I feel like being social, Fallout is what I play when I want to be immersed in my own world.
Hard Core mode should be retained, but kept optional, with the ability to turn it on and off at any time.
Finally, if a new location hasn't been picked, New York really needs to be done. The destroyed Statue of Liberty is the only Post-Apocalypse clynch fallout hasn't done, and besides, it would be awesome to listen to Sinatra's "New York, New York" on the pip-boy. That same song, with cutscenes from the game may also make a killer trailer.