Which factor played the largest role in the decline of the Byzantine Empire?

Answer: the recurrent debilitating civil wars.

Explanation: The Byzantine Empire when created when the Roman empire splitted into the Eastern Roman Empire and the Western Roman Empire.

The Eastern Roman Empire (Byzantine Empire) survived a thousand years after the collapse of the Western Roman Empire.

Constantinople which happens to be the capital of the Byzantine Empire was the most wealthiest, the Empire's territory extended through Eastern and Western Europe.

Recurrent civil wars played the largest role in the decline of the Byzantine Empire. After each civil war, a part or territory is lost and could not be fully recoverd until the next civil war which will lead to lost of even more territories. This greatly caused the Byzantine power and influence to decline drastically which was never fully reversed before the final collapse.