In Assassin's Creed Brotherhood, Ezio Auditore makes Rome his headquarters.
The game is set primarily in Rome during the early sixteenth century, where Ezio confronts the Borgia family and works to rebuild the Assassin Brotherhood. The city is divided into districts controlled by Borgia forces, and players liberate those districts by destroying military infrastructure and completing related missions.
Ezio operates from the rebuilt hideout on Isola Tiberina, an island in the Tiber River. The headquarters supports the recruitment and training of new Assassins, while the nearby city becomes a large open-world environment containing landmarks, shops, tunnels, and missions.
Florence and Venice are central to Assassin's Creed II, not Brotherhood's main base. Constantinople is the principal setting of Assassin's Creed Revelations. Brotherhood does include smaller connected areas outside Rome, but Rome remains its defining location.