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At first the stories appear to be poles apart: ACB is about a Master Assassin bringing about the fall of the Borgia Papacy, while Up in the Air is about a bloke sent by a firm to fire people on behalf of bosses too cowardly to sack their own employees. That bloke is portrayed by George Clooney, who like Ezio, famously possesses a Golden Age Hollywood charm despite getting on in years (and he even portrayed Batman, one of the inspirations for Ezio, in the infamous Batman and Robin).
However, both stories about men too clearly stuck in the comfort and luxuries their dirty jobs offer, when they should have settled down and started a family. Sacking someone may as well be tantamount to killing someone, and Clooney's character even spends his sessions councilling the newly unemployed, just as Ezio would always comfort their victims over their mistakes. Ezio basks in the subsequent cash he receives, while Clooney's protagonist enjoys the comforts of air travel.
Over the course of both stories, both protagonists make the mistake of falling in love with the wrong woman. Ezio of course fell for Caterina Sforza, who merely seduced him to ensure his loyalty in a failed attempt to gain his help against the Borgias from conquering Forli. In Up in the Air, Clooney's character, who realizes how hollow and cynical his life was, attempts a serious relationship with the woman he was casually hooking up with, even inviting her to his sister's wedding, only to discover she has a family, and that all he was was an "escape".
Up in the Air is well worth-watching, especially if you want to see comic actors like Anna Kendrick and Danny McBride stretch their dramatic muscles. PS. I acknowledge this title was total clickbait - in my opinion the best AC film never made is still The Matrix.