In Assassin's Creed Brotherhood, Ezio Auditore primarily defends Rome.
Rome is the main open-world setting and the headquarters of the Borgia family's power. Ezio works to weaken Cesare Borgia and rebuild the Assassin Brotherhood by recruiting allies throughout the city. The game's missions combine historical locations, political intrigue, and fictional Assassin-Templar operations.
Brotherhood is set mainly in the early sixteenth century and continues Ezio's story after Assassin's Creed II. It expands the series with recruitable Assassin apprentices, faction management, and a larger role for the rebuilt Brotherhood. The city includes landmarks connected with papal and Roman history.
Florence is Ezio's birthplace and an important location in Assassin's Creed II, so it is a frequent mix-up. Constantinople is the principal setting of Revelations, while Jerusalem is strongly associated with the first game. Brotherhood's central city is Rome.