One very huge different: BG series, NWN and even IWD (advertised to be the dungeon crawl-oriented offspring of the Infinity Engine) all involve a lot more story than D2, Dungeon Siege, or any game of the same ilk. This means you have dialogue choices that go well beyond accepting/rejecting a quest. For BG2, the NPCs that join your party will have personalities of their own, and some will leave you if you do not accede to some of their requests and/or have a vastly conflicting moral code. Some quests can be resolved via diplomacy and investigation rather than the "kill this, fetch that item" routine.
You don't need to know D&D rules (AD&D for BG/IWD), but familiarity with it will help a bit. On the other hand, if you're already experienced in playing RPGs, it shouldn't take too long to become accustomed to the rules. Some things are a bit more complicated than what you're used to -- charisma, wisdom, the persuade skill in NWN, and so on.
