In Assassin's Creed: Brotherhood, Ezio Auditore primarily liberates Rome from Borgia control.
Rome is the game's main open-world setting and the center of Ezio's campaign against the Borgia family. Cesare Borgia's forces and allies control districts of the city, and Ezio weakens that control by destroying military assets, eliminating key officials, and rebuilding local support.
The game expands the series' Brotherhood concept by letting Ezio recruit and train new Assassins. Recruits can be sent on missions across Europe or called into Rome to assist him, making the restoration of the Roman Brotherhood part of the city's liberation.
Brotherhood follows Assassin's Creed II and continues Ezio's story after his campaigns in Florence and Venice. Although the game includes the Villa Auditore at Monteriggioni and missions outside Rome, Rome is the defining setting. Constantinople becomes Ezio's principal destination in the later game Assassin's Creed: Revelations.