Challenge: Fourth Crusade type event happens to Rome

What would cause Eastern Orthodox warriors (not necessarily Greek) to ransack and take over Rome, setting up their own empire in the region?
 
Rome itself wasn't terribly important, as a city, and Pope often lived outside it during the middle ages.

Neither was Rome very defensible.
 
A reviving ERE gets too big for its britches and decides that Justinian was flawed in not having enough modern weaponry, not in concept.
 
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