I doubt the expansion will deal with the conquest of the americas, since there's barely any gunpowder infantry in the game, and some factions don't even have any. Adding a whole new era of units to the game would be too big for an expansion.

Keeping that in mind, I have no idea where they could go. Most major events after the end of the current game would deal with gunpowder warfare. They could possibly do the Hundred Years' War, or some kind of islamic invasion from the east, but those seem quite limited. Not much else stands out.