I'm currently playing HRE. One of the first things I did was take florence and then gift it to the Papal states in return for an alliance. This gave me a nice buffer from Sicily.

Then I simply wound up the Milanese until they attacked me and got excommunicated. Then I called for a crusade on Milan and took it the next turn. Then I did the same thing to the Venetians, culminating in the Sacking of Venice in the Crusade of, um, turn 30 or so.

Anyway, both these crusades left the Papal States with full stacks floating around and the gift of Florence must have woken their expansionist territories because the next thing I realise, when I send my Merchants out for rare resources, is that the Papal States have wiped out the Moors in North Africa and taken everything from Arguin to Tripoli.

However, they didn't expand much from there, even when Spain and Portugal were excommunicated and they could/should have taken their lands. Of course, later on, during my annexing of the Middle East, I dumped Damascus their way just as the Mongols hit Edessa. That seemed to work very well at distracting almost everyone for a while...