Make Italy considered a part of Eastren/Central Europe

In addition to the Byzantine-wank I have one other idea. You could have some distinctive sect of Christianity come to dominate Spain, France, and Britain- like Miaphysitism did in Egypt for example. Have this remain stable over the centuries and an opposition develops between this and the Nicene regions, eventually creating an East-West divide with Italy falling into the former category.

Arianism might fit the bill but my impression is that the Germanic conquerors never really succeeded in imposing it onto their subjects. A more plausible POD would be one that pre-empts the entrenchment of Nicene Christianity in those areas.
 
Personally I think a Byz or Otto-wank would do it. Either by conquest or luck.

Personally though, I like another option. A Venetian-era Byzantines. (Or just a super Venice).

Effectively never complete the independence of Venice. Have it remain nominally loyal, but easily the rival centre of power for Byzantine politics. Essentially the Republicans vs Imperials. Have both Venice and Constantinope work together, with the Venetian tradition flourishing whilst the traditional Byzantine system is hit again and again, whilst Venice grows in economic power, whilst it's loyalty to its Roman identity manifests as increased distance from the Papacy in favour of a Greek Rite in Latin.

At the right crisis, with Venice effectively the heart of an Exarchate of Italy (however small) able to experiment with its local government and expansion, is able to take the capital in a coup by the Doge. The committee republican brings the ideas of Venice to the heart of the Empire, and reforms it as an explicitly elective republic with merchants wholeheartedly embraced.

At which point the Grand Republic can leverage the economic might of a Venice writ large and begin a unification of what we'd today call south and central Europe AMD Italy. Creating a cohesive Empire from Italy to Anatolia.

This leads to a Europe split in four ways. Western Europe to the West of the Alps. Northern Europe in Germany, Scandinavia and it's overlaps in Britain (west) and the Baltic (east) with the east being defined as the lands east of the Vistula and Carpathians. Central (Or Southern) Europe being defined by this Greco-Italo-Slavic-Turkic hybrid republic as a Roman Republic.
 
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