The game begins right where Brotherhood left off: after touching the Apple of Eden and being forced to stab Lucy. Desmond falls into a coma and put into the Animus as a life support machine. He later awakens on an unusual island and runs into Subject 16, who informs him that the memories of Ezio and Altair need to be synched in order for him to return to his body or he will fall into a mental arrest.
He then goes back to relive the life of Ezio, who arrives in Constantinople, to search for keys left behind by Altair that will explain where to find an item that could end the war with the Templars.
You play as all protagonists through out the series but mainly Ezio. When you pick up a Masyaf key, you will go back to a certain memory of Altair and play through the level as him. Desmond is playable when the player goes to a gate on the island and you learn more about his past before he was abducted by Abstergo Industries.
Most of the game takes place in Constantinople; the streets are full of markets, town criers and guard patrols. The rooftops have zip-lines were Ezio can use his new “Hook Blade” to fly through the city faster. You can still buy shops, weapons, armour and equipment. There are treasure chests and you can still hire Mercenaries, Thieves and the new Romanies.
Going back to the Hook Blade; in combat, it can be used to trip up guards or an evasive move in which Ezio flips over their back. The Hook Blade also comes in handy on rooftops. With the simple push of a button, you can extend your reach, making it easier to jump between rooftops, and reach ledges that are higher and harder to reach.
You also now have the ability to craft different bombs like smoke, impact, coin and stink bombs. You can find ingredients for bombs in shops and treasure chests. You can then make some bombs at crafting tables in assassin's guilds and tables around the city.
Ezio can still recruit Assassins; you can train them up to Master Assassin level by sending them on missions. Levelling Assassins to Master will unlock the ability to put them in charge of Guilds, which they can then protect them from being attacked.
Throughout Constantinople, there are towers that are under control of the Templars. As long as they still have the Templar banner on them it will prevent you from buying shops in that area. To destroy the Templar influence you will have to resort in killing the leader and setting the tower on fire, similar to the Borgia Towers in Brotherhood.
At that point the tower becomes an Assassin Guild, and until it has a Master Assassin it's still vulnerable to being attacked. When this happens, you play a tower defence mini-game, this is a cool new feature where you place blockades in the path of soldiers and Assassins on rooftops which fire arrows and bullets at soldiers. You can also fire cannons, but after triggered it will have to recharge.