1) More emotional NPC's- Like Red Dead's reputation system with civillians, the NPC's will act on your Karma and rep i.e. if you are very evil then children, the old and women will run from you in fear where as if you are a good character then children will run next to you and cheer etc.
2) Factions- I love the idea of the Desert Rangers! If they get added then I'll buy that game the second it comes out. But I digress, like with Skyrim's major faction quests, it would be intresting if they took the same stance with F4, example: After their war with the legion, the remaining Desert Rangers who decided to remain independant of the NCR are fading into legend. The group is mixed between loyalists who wish to remain independant and those who wish to join with their brothers in the NCR. But enemies are everywhere and before the decision can be made the Desert Rangers must become powerful again.
3) More MOD's on weapons- Such as Red dots, ACOG's, thermal etc etc
4) More in depth Companions- Now if you have done Boone's side quest you should get why I love it. The character and the story is practically a game in itself. It really is amazing. So maybe companions in future could have a lot more thought put into their stories. Plus like in F:BoS maybe we could meet former PC's? or have them as companions. Since it's likely F4 will be in New York it would be cool to see the Courier in old age there too.
5) Town creation- I'd like to be able to set up my own settlement. Name it, build houses, employ farmers and workers, hire guards, join nations, conquer other settlements etc.