Dual Wielding: Because nothing is more hardcore than charging face-first into a Caesar's Legion patrol, Raider encampment, or Paradise Falls-type of place with two sub machineguns.
Admittedly, I think it would be great to see another one set in D.C., with more factions and whatnot. I think that would be amazing. Another trip to Point Lookout, an expanded Pitt region (Hoping for it, however unlikely), and maybe even a view of The Commonwealth. Admittedly, I'd be quite proud to see St. Louis, Missouri featured, or even some of Illinois/Iowa. (Why Iowa? Just 'cause.)
I could probably rant about what I'd like to see (more companions, freeform missions (randomly generated missions, like bounty hunter missions and stuff), more perks, etc.), but I'll spare the time and rant about it somewhere else.