In Assassin's Creed: Brotherhood, Rome is the main open-world setting for Ezio's campaign.
Brotherhood continues Ezio Auditore's story after Assassin's Creed II. He travels to Rome to challenge the Borgia family, whose power is concentrated in the city and whose leaders are tied to the Templar order. The game turns Rome into a large interconnected environment that Ezio gradually liberates.
A key feature is the rebuilding of Roman districts. Ezio can destroy Borgia towers, recruit citizens, expand the Assassin network, and restore shops and landmarks. This system makes control of the city part of the gameplay rather than merely a backdrop.
The Vatican and the Colosseum are among Rome's recognizable locations in the game. Florence is Ezio's birthplace, while Constantinople is the principal setting of Assassin's Creed Revelations. Jerusalem belongs mainly to the first game's Levantine setting, so none of those cities is Brotherhood's primary open world.