Technically speaking, against equal opponents, a first-punch knockout is an impossibility in 2e. If someone with damage +10 hits someone with toughness +10 it's impossible to miss by 15 or more to get the knockout. Even if the defender took 4 bruises they'd only have a 20% chance of being knocked out on the 5th hit. The best someone could hope for in that situation would be 2 staggered results in a row, which would then result in a knockout. So there is no way to take out an opponent in a "single blow" if the combatants are equals. Of course if you have the Powerhouse hitting the Costumed Adventurer that mismatch is going to possibly result in a one-hit knockout. Batman's not designed to take a full-force blow from the Hulk without some luck saving his butt.
Part of the beauty of M&M's damage system is that lesser threats are still valid against a foe even if they can't result in a fast knockout. The agents with the +5 blaster pistol can possibly get some bruise damage on a target who doesn't have impervious toughness. That's a big advantage over many other games.