Ultron: Can bypass the FiM villains' physical defenses by infecting and assimilating them, erasing their minds.
Obi-Wan Kenobi: The Force is external, and there are Jedi that can move black holes with it.
Ghost Rider: Can completely burn away any physical body with his Hellfire, fry any soul with his Penance Stare, then eat the soul.
Chuck Norris: Can roundhouse kick anything into oblivion. We all know how powerful this kick is. There's also no escaping from Chuck Norris.
Sapphie: This anime version of Twilight Sparkle is a science wizard who uses technology as well as magic. The FiM villains' anti-magic is obviously useless against tech. Sapphie has also survived an explosion that was visible from orbit, a fall from space, and a punch strong enough to send her back to the planet to begin with. By the end of the original Jewelpet anime (prior to my planned reboot Jewelpet Magic Black), she can make infinite copies of herself. Unlike the actual Twilight, Sapphie doesn't need artifacts to take down major villains. In addition, Sapphie has a human form that doesn't take away her magic but empowers her.
Kirby: His power is canonically infinite.
MegaMan.EXE: Destroyed and recreated Cyberworld, an entire universe complete with stars and galaxies.
Ruby/Luea: 10 billion weapons, both physical and magical. Can run long distances in six seconds. Durable enough to survive explosions that are visible from orbit. Luea is not only the equal of Ruby, but has also manipulated memories, disabled physical defenses, and turned someone into a toothpick. Also like Sapphie, both Ruby and Luea have human forms that give them boosts instead of taking away their magic. Elements of Harmony? Ruby and Luea don't need those! And last but not least, Luea is far more fit to rule Jewel Land than Twilight is to rule Equestria.
Wally West: Can break fate and literally punch stuff out of existence. He killed Death itself.
Beerus: One word: Hakai.
(There are obviously many more applicable characters that I don't know about.)