I'm gonna say the failure to defeat the Soviets in the Winter of 41. Stalin was on the ropes, and seriously considering negotiations. He moved the entire government east in fear that the Germans were going to seize Moscow.
Had the Germans taken Moscow, Leningrad would likely follow due to a resulting incapacity to supply Leningrad because of Moscows status as the rail hub for all of European Russia from the trans uralic factories. Furthermore, the morale shock would have been terrible to lose their two most important cities.
After that first winter, the Soviets were on war-footing, and were safe from outright defeat. They might consider a negotiated peace, but as long as the Soviets were safe from outright defeat, the Nazis were doomed, IMO.