Casey Jones and April O'neil in Genesis version. The latter because she abandoned the Damsel in Distress role to be more of a fighter like in the comics.
The SNES version of the game itself can be counted as it is quite popular among tournament fighting game players.
Game-Breaker: There are a few moves that are a bit too good. Donatello's strong punch has instant recovery, deals tons of damage, stuns fast, fills um 40% of his special gauge when his life is on red, AND has very good range. The computer can counter this by magic reflexes, but against a human...
Leonardo's 'Millennium Wave' takes pretty much the whole screen, deals around 45% damage IF BLOCKED. But if it connects, it deals up to 90% more AND stuns the opponent.
Michaelangelo's Rising Thunder takes over 30% of life if it connects on the ground.
Raphael's biting grab in the NES version can be spammed to make getting through the game trivial.