The embodiment of trial and error and the ultimate test of patience and memory, defeating Mike Tyson is perhaps the single biggest example of a game's control scheme being pushed to its absolute limit against a boss that requires complete devotion to defeat.
Already Punch-Out!!'s feel is a tight mix of left/right dodges and attacks, learning when different foes are going to leave themselves open and wading in accordingly. Just learning when there's a break in the onslaught of haymakers Tyson provides is hard enough - then being able to execute on that repeatedly is where the real challenge comes in.
It goes without saying that because Iron Mike was heading up the marketing materials, he needed his in-game reputation to be just as fierce as when he strolls out to the boxing ring, but this?