1) Yes. The main one will be somewhat obvious in-game. Explore everything, feel free to put the main plot on the backburner.
2) You will reach new areas and have your ass handed to you. Probably. Unless you're just that good/have the difficultly too low. Crank up the difficulty if you're too powerful. My experience was levels 1-9 I was weak and scared, levels 10-18 I was like "I am a god!" after that it evened out.
3) Yes. But there are some handplaced set items AFAIK.
4) No.
