Which Assassin's Creed game first made Rome its main open-world city?

Assassin's Creed: Brotherhood first made Rome the series' main open-world city.

Released in 2010, Brotherhood continues Ezio Auditore's story after Assassin's Creed II. Its central open world is Rome, where Ezio works to weaken the Borgia family and rebuild the Assassin Brotherhood. The city is divided into districts that can be liberated from Borgia control.

Brotherhood expanded the franchise with recruitable Assassin apprentices. Players could train recruits, send them on missions, and call them into combat. The game also introduced a persistent multiplayer mode, a notable addition to the series at the time.

Assassin's Creed II includes several Italian cities, but Rome is not its sole main open-world setting. Revelations later moves Ezio to Constantinople, while Assassin's Creed III focuses mainly on colonial cities and wilderness in North America.