Italy
Frederick II
Any history of late medieval Italy must take account of Frederick II, Holy Roman Emperor. His name was Frederick of Hohenstaufen and he looms large because he came closer than anyone to bringing all of Italy under his sway.
He ruled both Sicily and Kingdom of Italy, at least in theory, and he spent much of his life making that theory a reality. He drew heavily on the resources of Sicily to conquer the north, with mixed results. The papacy became obsessed with thwarting him, and eventually with destroying not only Frederick but his entire family. The popes largely succeeded in this.
The battle against Frederick was not waged by the popes alone. The northern cities likewise resisted him, though some allied with the emperor. All of Italy aligned on one side or the other. Ancient local feuds were bound up with the larger struggle.
Frederick was excommunicated in 1227, reconciled in 1230, violently condemned in 1236, and excommunicated a second time in 1239. He was actually deposed in 1245, though no pope was able to make the deposition a reality. He died in 1250.
It's difficult to overestimate the importance of Frederick II to the history of Italy as wel as the history of the Empire. He was a forceful personality and introduced many innovations. Under his rule, the Empire was without a doubt at its very pinnacle of prestige and authority. This very success, however, called forth oppostion at every turn.
The long-running battle between the emperor and the popes, most particularly Gregory IX and Innocent IV, was deeply disruptive for Italy. The conflict went on from its beginnings in the 1220s well beyond Frederick's own death—perhaps sixty or seventy years, depending on how one defines the conflict. By the end of it, everyone had chosen sides; everyone in Italy supported either the pope or the emperor. Even those who didn't actually care much one way or the other had to pretend to choose. Neutrality was not an option.