This brings up a point me and a friend discussed. Now that they've introduced guns, one of two things can happen. 1: They introduce more advanced guns to the mechanics, or 2: A heavier penalty for lack of stealth, seeing how you lack guns.
Either one is sure to cause complaints, but personally, I'd prefer 2.
OT: I'd say going back and forth from Russia and America in the Cold War, working undercover in either the CIA or KGB, but in reality, spying on both sides for the Assassins. Plus, players could do some actual black ops or assassinations.
Option 2: WWI England. Y'know how Altiar screwed up the first mission in AC1? How about the Assassins try to stop the Templars from assassinating someone at the start of 3, but fail? Considering the era, take a guess who the target is.
Edit: Wait, those were just locations for future games. 3 should continue in present time.