I think seeing a BG3 in 2.edition would be impossible. I have no doubt that it would be made using the latest ruleset on the market at the time of development. (currently 3.5 edition)
NPCs is always the sore point - in my opinnion - in cRPGs.
NPCs needs to be alive - thus I would really love to see a game where they move around and interact with each other and the game world. Also - I'd like to see various factions amongst the NPCs, so that if you help faction X alot, faction Y would be reluctant to have anything to do with you.
NPCs *need* to be alive otherwise the world can very quickly get a static feel where the PC is the only one "alive".
More races would be nice (although I always play human) - but I'm getting (pardon my language
) sick to death of drows. I'd like them to be somewhere else in the story - and please get them to take Drizzt with them
The storyline is the hot item in a possible BG3 - there are many pitfalls if they are to be somewhat relevant to the BG-series in more then name.
But a deep and epic story would be nice, however - what it should be about is difficult matter.
What I would really like to see - is some depth and scope again. Since BG2 most games "boats" of a 40-50 hour campaign. That is simply not enough if the game is to be focused on single player. I don't know why this standard has become de facto, but it annoys me tremendously. Take ressources from graphics if extra is needed, but please provide an epic game in both depth and scope.