In Assassin's Creed Brotherhood, Ezio's main base is Rome.
The game is set primarily in Rome during the early sixteenth century, where Ezio works to weaken the Borgia family's control and rebuild the Italian Assassin Brotherhood. Unlike Assassin's Creed II, which moves between several major cities, Brotherhood concentrates most of its open-world activity in one large urban area.
Rome includes famous landmarks such as the Colosseum, the Pantheon, and the Castel Sant'Angelo. Players liberate districts, recruit new Assassins, and restore shops and services as Ezio's influence grows. The city therefore functions both as the setting and as a progression system.
Florence and Venice are strongly associated with Ezio because they feature prominently in Assassin's Creed II. They are not Brotherhood's main base, however. The Rome setting also explains the game's title: Ezio is not merely acting alone but is organizing and expanding the Brotherhood in the papal capital.