The changes I would like to see largely involve getting rid of unnecessary tedious crap to allow the game to be more fun.
I think the changes I'd like would have to wait for a new game, because of how integral all of these things are to how the game works, but here they are:
1. Less loot. Remove junk loot from the game completely. Looting every corpse is a chore and gets in between me and the fun parts of the game.
2. Scale wayyy back on the resource gathering. Gathering resources is awful and gets in the way of fun. Running around searching and stopping to pick flowers and gather rocks is not heroic. The Inquisitor should have people to do that crap for him/her. Locating resource "nodes" that produce resources would be better.
3. Bring back if/then tactics. I really miss them.
4. Do something- anything- about the terrain. I haven't seen a game deal with this one well yet, but one thing I absolutely despise about open world games is trying to get from point A to point B and having to run up hills and jump to see if I can make it. This is frustrating, stupid, and a total waste of time.
I realize that by reducing loot, reducing gathering, and trying to limit travel frustrations, I am probably taking 30 hours out of a single playthrough. But I'd rather have 30 hours less mundane crap to deal with in order to enjoy the many, many excellent parts about this game.