From a tactical perspective, Ludendorff's biggest mistake in my opinion was Operation Michael. Strategically, he should have sought to end the war on favorable terms, rather than trying to win an all or nothing absolute victory.
1918 actually began quite promisingly for the central powers.
And given Ludendorff's goal to bring the war to an end... and that he had the initiative in 1918, the question became what to do.
The Western Front was the main front, a victory would end the war in Germany's favor. (High risk, high reward) But there were a lot of entente forces there and the reinforcement barely gave the Germans a numerical edge. Besides, the Germans were in the heavily fortified Hindenburg line. And there was no reason to believe Germany couldn't hold the allies there in another year of defense. As it unfolded, Michael's biggest problem was it was unfocused, without a specific strategic goal.
A Michael scale offensive in the Italian front in 1918 was another possibility. The problem is that Italy is a large and mountainous country, and in theory the entente could have just retreated south and absorbed the blows and, therefore, tied down the fresh forces.
A Michael scale offensive in the Macedonia front in early 1918 would have made the most sense. A victory there could have stabilized the Bulgarian regime. It was also a relatively thinly manned secondary front that was far from entente's supply lines. 500,000, or even 250,000 extra German troops could have given central powers a crushing advantage. if that front could be eliminated all together, it could have yielded massive bounties in equipment and men, and it would have freed up a lot of men for action else where.
So from a strategic perspective, it was Ludendorff's mistake to try to end the war in an all of nothing gamble in 1918. He should have small-balled the entente. Won in Macedonia. Then worked with the Turks to take the Suez.
Sure the Americans would have arrived in great numbers. But that would be a problem for 1919 ...