Rome is the city chiefly controlled and explored by Ezio in Assassin's Creed Brotherhood. The game continues Ezio Auditore's story after Assassin's Creed II and focuses on his campaign against the Borgia family.
Brotherhood is set primarily in Renaissance Rome, where Cesare Borgia and his allies exert political and military influence. Ezio works to weaken that control by liberating districts, rebuilding shops and landmarks, recruiting Assassins, and dismantling Borgia operations. The city therefore changes as the player progresses rather than remaining a static backdrop.
The game also includes a short sequence in Monteriggioni and a modern-day storyline involving Desmond Miles. Its title refers to Ezio's effort to organize and train a larger Assassin Brotherhood, not to a city or historical faction.
Florence and Venice are major locations in Assassin's Creed II, which is why they are common alternatives. Brotherhood shifts the main Italian setting to Rome and expands the series' city-management and recruitable-Assassin systems.