I can see adding Milan as a goal, I believe it was considered part of the HRE at some point, but conquering Rome would bring down the rest of the Catholic world on HRE. I believe if Rome is taken the Papal States (where ever they might end up) initiate crusade after crusade to retake it. While it might be fun to take on the world in the late campaign, leaving Rome alone provides for more opportunities for Crusades to exotic places and not having half the avatars in the PBEM burned at the stake for Heresy. Inquisitors are not fun, particularly with weakened assassins in 1.1.

Of course I would love to see the debate that occurs in the Diet when the "Let's take Rome" motion is proposed.