Nothing is True. Everything is Permitted.
Spoilers below:
Each Assassin's Creed game has a theme, usually something poetic or ironic.
In the first Assassin's Creed, Altair didn't follow the codes of the Assassin Order, which nearly got him and all his companions killed. He was reduced to a mere recruit, and had to do a variety of tasks implied to have been then anything else he had faced up to that point. The phrase comes into play when, at the climax of the game, Altair is betrayed. He was lead to believe his quest was a fight for justice, when really it just bettered the goals of a tyrant.
Nothing Altair thought was true, and when everything went to crap, Altair had to do anything permitted to save his fellow Assassins.
Assassin's Creed II has a similar premise, with arrogant rich kid Ezio getting his life shattered.
He almost became just like his enemies, letting his anger and lust for revenge take hold of his life, and he just barely lets it go. The Templars continue to expand and the Assassins continue to dwindle in numbers, as if the conflict is a cycle that can't be avoided and Ezio is ruining his life getting in the middle of it. He matures and realizes that revenge isn't the answer. This allows him to move on in Revelations, where he finally gives up searching for answers, and comes to accept things as they are. He had no reason for continuing, and was finally able to be at peace.
In Assassin's Creed III, the player is lead to believe Haytham is the mentor for Connor. We've played them both as "good guys", why not?
Even when it becomes obvious Haytham isn't an Assassin and is really The Big Bad, most players didn't pay attention, because "Hey, this guy is Connors dad, so he must be good, right?". Wrong. Haytham was a Templar, and the whole first half of the game was you making things worse for the protagonist faction. In that way, "Nothing is true" comes in again. The player is also lead to believe that the game is "Good guy versus Evil Guy", but they'll find that hard to accept when the "bad guys" are the people you just spent the first three sequences completing. They each had a reason, and Connor wasn't always right. In fact, by the end of the game he's not really fixed anything, and has only made things worse. The whole game was a mostly hopeless battle that didn't even matter.
The whole series is a gigantic irony of games.
