Has Jim Mattis ever met he war he did not support? Including the illegal, endless ones? I thought so.
I think the draw downs in Syria and Afghanistan are the nails in the coffin reasons behind the resignation. He was Tillerson in uniform but has the discipline to keep his mouth shut for the most part. Mathis and Tillerson were still trying to save the old post-WWII order despite it fraying and not adapting to a changing world situation, even if it means America continuing to be screwed.
The lack of perpetual war will drive the globalist, neoconservatives and NeverTrumpers insane. If Trump appears headed for re-election they will attempt to take him out, bet the farm on it.