What was the most significant factor that led to the collapse of the Western Roman Empire?

The most important of these was the fact that the Western Empire had not had a functional and intelligent ruler since Constantine the Great, and he divided the Empire and moved east during his reign. This left Rome governed by a series of Generals who were more concerned with fighting each other for the throne then with actually steeming the tide of the problems assualting Rome. Had Rome had an effective Roman ruler, the Western Empire might have survived politically, although it probably still couldn't avoid many of the cultural changes that occured in the fifth and sixth centuries. But, Rome had no effective rulers, and this weakness made every other problem worse.

Invasion, economic decline, and eastern Rome was doing better