When I play the Italians at some point I have to invade Rome
and stop him from meddling with my plans. Then I instigate a rebellion in Rome, and I train the rebels by sending my traitor generals against them one at a time. When the Pope comes back he has to deal with the rebels first and usually forgets to attack me, also I get to keep the Pope Provinces.

If my faction is far away from Rome I prefer to leave the Pope alone and wait for him to excommunicate someone, so I can step in and invade their lands.