Welcome to the Specultorium, where facts are non existent and the loudest person wins.
Since the ongoing theme of the games is the Templar's attempts to maintain control of humanity (to guide us to a future that can survive a catastrophic event in the far future?), the arc of an Assassin's Creed III trilogy would have to be about taming the newly independent republics in the Western Hemisphere, probably from within.
Shays Rebellion/Whiskey Rebellion? That would reflect the theme, but that may occur too soon in the timeline to be one of the sequels, maybe lost memory DLC?
Arg, I'm sure I'm not thinking outside of the box enough. The Louisiana Purchase! Travel with Ben Franklin to Paris (a new setting), kill some people, results in Paris selling all that land. Thats about 25 years after the Revolution, maybe too far, or maybe that is the third game.
I bet in the second you go to England, London is the City. You could get away with just the one city, like with Rome.
Will they address Slavery? That institution probably suited the Templars, but I don't know if Ubisoft has the stomach. Then again, think about the ending to ACII.