In Assassin's Creed: Brotherhood, Ezio defends Rome as an Assassin leader.
Rome is the principal setting of Brotherhood, which follows Ezio after the events of Assassin's Creed II. The city is controlled by the Borgia family, led by Rodrigo Borgia and his son Cesare. Ezio works to weaken their power while rebuilding the Assassin Brotherhood.
The game expands the series' city activities with recruitable Assassins. Ezio can train allies, assign them to missions across Europe, and call them to assist during encounters. This leadership role is a major difference from his earlier journey through several Italian cities.
Florence and Venice are important locations in Assassin's Creed II, not the main city of Brotherhood. Constantinople becomes the central setting of Assassin's Creed: Revelations. These overlapping Renaissance locations are a frequent source of confusion.