The Australis rollout was a massive controversy at its time, and so was nuking the old extensions in favour of those using Chrome's standard despite most functionality having no replacement in the new API. They also didn't bother implementing AD group policies for a very long time, which lost them all (or maybe just most) corporate use cases.
There were also a bunch of smaller ones along the way; I left FF when they made self hosting your own sync server virtually impossible.