Mike Tyson's Punch-Out!! was one of favorite games growing up. I'd dust it off at least once a year and play through it multiple times from about the age of 10-18. During that time, I could definitely beat Tyson the first go. Sometimes I'd just pop the game in and 007-373-5963 (that and the Konami code will be permanently etched into my brain) and go straight to Tyson, but I've also done the full run more than once.
As an adult? I don't think I've beaten Mr. Dream as an adult. I say Mr. Dream because I haven't actually played my old Mike Tyson NES cartridge since I moved out of my parent's house. I've tried multiple times, but I just can't do it anymore. I think one of the most difficult things is trying to be honest with myself and figure out which of the following is the culprit:
1.) I'm just out of practice and I could totes do it if I dedicated a little more time to it.
2.) There's input lag via the Virtual Console and HD sets that didn't exist when using a real NES controller on a real NES hooked up to a CRT TV.
3.) I just don't have what it takes anymore as my reflexes aren't what they used to be.
It's probably more of 3 than I'd care to admit. But I'd like to think that 2 is a legit factor.