While it was a progressive fall, there were a few moments that could be considered the 'point of no return'. But considering each of these is spread hundreds of years apart, it just goes to show the Byzantines died a very slow death.

First of all, the Battle of Manzikert between the Seljuk Turks and the Byzantine Empire, which resulted in Roman defeat and the capture of the Roman Emperor, Romanus IV Diogenes. Although it's not considered a disastrous defeat for the Byzantines, it's still considered a huge step back. The Byzantine defeat at the Battle of Manzikert signaled the moment the Turks knew the Byzantines no longer had true authority over Armenia and Anatolia. And the Byzantines would never reclaim all of the land they lost as a result of this battle.

I think most historians agree that the sacking of Constantinople during the fourth crusade was the final nail in the coffin for the Byzantine Empire. The Byzantines were never able to fully recover from this, and never reclaimed all the territory they had before the sacking. They were left smaller, poorer, and their weakening power increased the influence of Anatolian Turks, most notably the Sultanate of Rum. And subsequently, the Ottoman Empire. By the time the Ottomans had conquered Constantinople in 1453, the Byzantine Empire had never really recovered from the Fourth Crusade.