Make most, if not all of the Italian peninsula and nearby islands considered to be a part of Eastren Europe rather than Westren Europe. Make it majority orthodox too and the Catholic Church can set up its headquarters in Spain or France instead.How would culture and society change? How might the Reninsance, age of discovery, the napoleonic wars, the world wars and the Cold War end up with this Eastren European Italy? Use any POD you like.
EDIT: You can also make some parts of the Italian peninsula eastren european. That way Rome could still be the headquarters of the Catholic Church.
EDIT#2: You can also put it in Central Europe if you prefer, just not Westren.