We've yet to see Skills in any form, but shouldn't they be more than just numbers? This also ties into the same question: What makes a good quest? Special quests are far and few as most of BGS games have you run errands or go from point A to point B and back to point A again. I think unique quests built around skills would make for memorable gameplay that stands out. Dungeons designed around skills can change up the gameplay, whether you're proficient at them or not.
You the Sneaky type? Why can't a dungeon be based around stealth and put you through the test... and even if you're not the sneaky type and rather good with heavy weaponry, you could still get bested if you go guns-a-blazin'. Vice-versa, have a hideout that actually is much faster paced than normal.
I think what makes quests more meaningful is having an actual theme to them. Construct bases and forts around particular skills, most of them without actually being required to be advanced in those skills, but challenging if you aren't.
Tie that in with quests that make you figure out things on your own without pointing you in its direction (aside from hints from terminals or holotapes or the quest giver) and that would make the game for me. The detail of the world will already be good enough, now don't make it play like a chore.