She certainly didn't help things. Her and John were basically attached at the hip and her presence and her influence on John certainly did become a substantial problem, but it was only one of many things. It was totally invertible anyways, but if I was going to pinpoint one happening it would be the death of Brian Epstein (and the vacuum it created). They held on for a couple years after it happened, but it was from what I understand, the biggest domino. Probably followed by creative direction and ego conflicts and then things like Yoko, although it has been said that she may have represented the biggest of the final straws.
As much as I'm definitely not a Yoko guy, I do think the fact that she is painted so much as the villain historically is very unfair. I think that it would have crumbled either way, she may have just poured a little gasoline on the situation.