Frederick II renewed the argument that had been going on since the time of Otto the Great - Emperor or Pope? This time there would be a solution one way or t'other. Meanwhile the unity of Christendom itself was under threat - ironically from one of it's greatest thinkers.
Frederick II - Stupor Mundi
Frederick II was the last effective Hohenstaufen, though the line of Barbarossa did not end until Conradin's death in 1268. Frederick was a child of Sicily, despite his life's mission to keep the Holy Roman Empire together, and establish the supremacy of the Emperor over the pope.
This meant he was a rather exotic mix of East and West; his menagerie, harem and muslim bodyguard were distinctly un-christian. Despite his talent, Frederick was never quite trusted.
For many years after his accession to the Imperial crown, Frederick managed to keep the Pope from the door as it were, by promising to go on Crusade. But when he did finally regain Jerusalem for the West - by negotiation - his bargaining chip had gone.
Just like Barbarossa, the key to the Empire was Lombardy in northern Italy. Despite early success, defeat at Parma in 1248 effective finished his cause and that of the Hohenstaufen.