I have about 5 hours into the game at the time I'm blogging this. I haven't much wandered too far off-course. My first run is always one where I stick close to the main quest.
From what I've encountered so far, there are quests galore. Simply walking through town and eavesdropping, you could already get a sense that there's a lot going on, people need help with various tasks and a lot of things to do in this game.
I'm really happy with the new skill tree (they call them perks now) -- very elegant, very beautiful and befitting of this epic fantasy world. It is the best improvement imho. They have completely revamped the character creation -- there are no longer classes and no more major/minor skill choices at the beginning. I think we are all better off since everyone tended to choose the same few key skills, resulting in generic and predictable builds.
Melee has improved, feels less like hitting tin pots and more like you are hitting flesh and bone; spell-casting needs a bit of getting used to.
Quests actually feel like those of Fallout 3, where one thing can lead to another and what seems like a routine "go fetch" can turn into something amazing and memorable.
There is more crafting in this game. You could use materials to make weapons and armor, improve on them.
Graphical glitches do exist, there's a slight lag in certain places as it loads up but no floaty characters or odd outlines. Character faces have improved. Character dialogue has improved as well, less nonsense. (I miss the mud crab talk.)