Which Assassin's Creed game is set primarily in Renaissance-era Rome?

Assassin's Creed Brotherhood is set primarily in Renaissance-era Rome.

Released in 2010, Brotherhood continues Ezio Auditore da Firenze's story after Assassin's Creed II. Ezio travels to Rome, where the Borgia family controls much of the city and the Assassin rebuilds a local Brotherhood to oppose them.

The game includes historical figures such as Cesare Borgia, Rodrigo Borgia, and Niccolò Machiavelli. It also introduced a major version of the series' Assassin recruitment system, letting Ezio train allies and call them into missions. Assassin's Creed II visits several Italian cities, while Revelations is centered on Constantinople, so Rome's dominant role identifies Brotherhood.