So, now mankind has been both saved and defeated by the first civilization, and more specifically, fallen under the control of Juno. She now utilizes the power of the Apple of Eden to rip away free will of mankind and enslave them to do her bidding. The only people left who have not succumed to its influence are, surprise, Templars and Assassins, who share the blood of the First Civilization, and more specifically, Adam and Eve.
So, let's look at Japan. *The Tokugawa period was prosperous and peaceful and Japan terminated the Christian missions and cut off almost all contact with the outside world.* Why not have this attributed the Assassins, whom by cutting off the Chrisitan missions, have also cut off the Templars from entering the country, and in turn they become complacent, and corrupt, because they have no true enemy or cause. No 'check' if you will.
This would be a reason that this time period and place would be of importance, because it would be a lesson from Minerva, on how the Templars and the Assassins need to be at peace, otherwise Juno will enslave humanity forever, and destroy the Templars and Assassins before they can destroy her. A common cause for two sides.
Further in the story... maybe Eve was the first Assassin, and Adam was the first Templar...? Their harmony can be used to show the ability of the two sides to come together.
I think that there were hints towards causes aligning in AC III, and that these can be expanded upon in the next entry into the series.
How about other ideas to toss around? I mean, part of the challenge that I see in the series is to be historically accurate with events, and to somehow figure out a way to make it believeable that the characters that are central in the game, belong in that period. There are events in history that cause them to become assassins.