-A story more similar to New Vegas than Fallout 3.
-Multiple starting points. The Fallout series houses an expansive lore, with lots of different types of people. Let me get the chance to experience the story from different perspectives. Maybe I start out as a raider, maybe I'm a vault dweller, maybe I'm a ghoul.
-Better developed characters that I actually give a damn about.
-The ability to shape your story, I shouldn't be shoehorned into being the savior of the wasteland if I'm playing as an unrepentant psychopath, and "good" characters shouldn't want to associate with me so readily and assume that I'd be willing to help them in their noble pursuits.
-Non suicidally idiotic party members, who can jump on top of freaking rocks. Hell, you could have them instantly teleport to your location, I would accept that too. Just don't make it so that they take the long way around just 'cause I jumped over a boulder.
-And on the note of jumping, I'd actually prefer it if they took the series out of first person mode and made it control more similarly to Uncharted or Tomb Raider or Assassin's Creed, at least when it comes to moving about the environment. I'd prefer not to bunny hop my way up a mountain. Plus it would be really cool to explore the post apocalyptic wasteland in such a manner.
-Failing that, make a better third person view, and make it actually possible to fight with ranged weapons.
-People talk to me when I want to talk to them. This is more of a Bethesda style game problem, than a Fallout exclusive problem, but I'm tired of wandering into town and having everyone stop in their tracks and blab the same 3 lines at me all the time.
-Less randomized AI patterns, at least when it comes to the civilians. This goes back to glitches, I've seen the randomized AI patterns result in people getting stuck between walls or throwing themselves off high platforms. It kinda kills the immersion, is what I'm saying. Hell, I'd be content with people just staying in one place.
-Better RPG aspects.
-Smarter enemies, especially for those who enjoy stealth playthroughs.
-I liked hardcore mode in New Vegas, that can make a comeback.
That's all I can think of for now.