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LMU Uncle Alfred said:
Can AC2 stand on its own if you've never played an AC game before?

most AC games (especially the earlier ones) have two storylines. One with usually Desmond in present time and one with the main character during the ancient times.
Now you won't have a problem at all with the Italian renaissance setting, as it's the first appearance of the Ezio character.
You probably won't quite understand the Desmond part of the story, but that's not the main focus of the games, so it's not much to worry about.