I actually would like to see no VATS. I used it plenty on my first play through, but on my 2nd I never once used it and I felt the experience was much better. I don't mind it for the occasional intense situation to pop a couple heads but generally I didn't like it... basically takes the fun out of combat.
I would like to see a lot more quests to do. I really loved Fallout 3 and some of the side quest lines, but I think when I go exploring new areas just for fun, it would be great to actually have something to do than just scrounge around for ammo and supplies... like yea, thanks for wasting 20 minutes walking out to this wierd building so I could find some shotgun shells and a health pack... greaaaat.
I really liked weapons and crafting your own, but I would really like to see more customizing on weapons. I think it's cool that you find the schematics and have to scrounge for parts, but they should add tons of schematics for different types of addons for every weapon - scopes, silencers, and pretty much anything from the BioShock catalogue. Of course, you shouldn't be allowed all the addons at the same time but certainly with high level skill you could get at least a couple on each weapon.
Considering it's vegas, it would be great if they make a casino with tons of different minigames just for shits. Like card games (or dice poker from The Witcher) and slot machines. I would like to be able to drive a vehicle too if it's a huge area like Fallout 3 was. Especially if I have to scrounge for fuel.
Excited about the hardcore mode. That's my style.