I don't know if you mean the current gen, but in XY Will-o-Wisp defensive Mega-Charizard-X appeared out of nowhere and started tearing up its regular counters. It had mostly been run as a bulky DD sweeper until then.
Back when Aegislash was in OU, it developed a horribly annoying SubToxic set that was quoted as one of the rationales for banning it (the pokemon that took on regular Aegislash would lose to the Toxic version). From what I can see, Toxic is pretty common on it now in Ubers, but that wasn't always the case.
Back in BW, there was a Leftovers SubDD sweeper Gyarados set that ran Fly so it could get past Ferrothorn. Nice bonus was extra Leftovers turns while in the air. I believe it was Sub/DD/Fly/Waterfall.
Back when Eviolite first came out, it took people a bit of time to clue into Eviolite Chansey being better than Blissey.
Shit, I remember when SpDef TTar was a huge innovation. I remember discussing it as a batshit crazy theory back in DP, and by BW it had become more or less standard (alongside Scarf) as a check to the newly introduced Flying spam.
Choice Band Ferrothorn was a thing and its Gyro Balls really hurt.
If you're looking to develop your own creative set, the best place to start is by scouring the movepool and stats of the pokemon in question and seeing if there are any alternative applications. Can a normally bulky Pokemon go offensive? Are there moves normally not being run that can give you a leg up on a potential counter or improve some matchups? Something I ran into recently that cleaned my clock was Assault Vest Hoopa-U. Shit took like 35% from my Gengar's Never-Ending Nightmare and one-shot me.