Gonna try and keep most multiplayer discussions here.
So we've seen that the new SimCity has a multiplayer side to it.
What is known/clear (List subject to change, check back every so often!):
One to sixteen (1-16) player support Cities will directly influence neighbors, including pollution
Another thing to point out is that the game does have a single player mode. The Online Only reference on the info page would most likely refer to product activation/registration only - Origin's all caps heavy legal statements seems to indicate this.
EDIT 3/13/12