Your challenge, should anyone chose to accept, is to have Cesare Borgia remain a Cardinal and be elected Pope. Bonus points for him succeeding his father,Pope Alexander VI.
Have Cesare see the Papacy as a way of gaining power over Italy, and he kills enough people to have him elected Pope.
An earlier death of Ezio Auditore da Firenze may help.
Sorry, obligatory Assassin's Creed joke.