Personally I think his win against Merciless Ray Mercer was his greatest win. He was way past his best and yet he dominated one of the best contenders in the division.
Yes that was a good victory for Larry,at that point in his career. For me, it's the Ken Norton win. He came in as the underdog and fought a Norton that bitterly wanted to hold on to the belt. It's one of the greatest heavyweight fights in history. It propelled Holmes on to the heavyweight scene.
Witherspoon or Norton overall. The Mercer win might be his most impressive, similar to Foremans win over Moorer.