You get a basically gauranteed excommunication during the first years due to Papal State rivalry.
Well, it is not that bad. Anyone can be Papal Controller at start (as I remember), and Pope will excommunicate Florence only if he is the controller.
Moreover, if you have 50+ relations with current Papal Controller, he will eventually lift any excommunication (IDK what it depends on, but seems similar to leaving Coalition).
Yesterday, for fun, I managed to take 2 provinces, release Urbino, left Avignon for attacking Provence, and Romagna for Ferrara.
One war with Ferrara (as co-beligerent, ofc--to core HRE provinces while at war), and Pope (left with Roma only) quickly turned from Rival attitude to frightened
and I enjoyed Italian +2 papal influence bonus
Then I got destroyed by double anti-France war (I can't say no to defense calls), but that's another story
I am also not sure whether Pope can excommunicate during his war, or whether he can excommunicate two countries in a short period of time.