Rome is the main setting for Ezio Auditore's story in Assassin's Creed Brotherhood.
The game follows Ezio in Rome during the early sixteenth century, where the Borgia family controls much of the city through political power and military force. Ezio works to weaken that control, rebuild the local Assassin Brotherhood and confront Cesare Borgia, the game's principal antagonist.
Rome functions as one large interconnected environment rather than a campaign spread across several equally important Italian cities. Its districts begin under Borgia influence and can be liberated as Ezio destroys towers, recruits Assassins and restores shops and landmarks. The city therefore changes visibly as the player progresses.
Florence and Venice are especially important in Assassin's Creed II, which is why they are common mix-ups. Brotherhood instead concentrates its historical action on Rome, with a smaller number of missions taking place elsewhere.