Verse Equalization is something of a double-edged sword. Some people might get the wrong idea.
I would say that, in a battle between Light Yagami and a goomba, even if Light learned his name (
"Don't call me Flunky!"), he still couldn't kill him because the Death Note is a weapon used by the Shinigami to harvest human life and the goomba's life is both inhuman and bound to the Underwhere. I'm also not so sure as to the biology of goombas and whether or not they can have heart-attacks, which in and of itself would limit Light's ability to make the death quick and snappy while the little mushroom goblin attempts to rush him. To me this makes sense for Light, as his whole shtick is that he's a fairly normal young man with an instant-kill technique with half a million restrictions that he's learning to get around.
Things get foggy, however, with cosmic absolutes like the Force. Can Darth Vader choke Fire Emblem's Black Knight if he comes from a 'verse without midichlorians? Logically, no, but that's no fun for Vader and it goes against Star Wars' "The Force is everywhere," mentality! So I would rule that, like StarDestroyer.net, the Force would still work.
So it's a matter of specific vs general. Now then, onto defenses and weaknesses.
If the character in question is someone like Ganondorf who can only be defeated by (or, according to this site's opinion as spelt out in Dungeons and Dragons terms, "Has really high damage resistance to everything except") holy items on account of his incredible power and divine backing, then I would say that any holy weapon would be able to do some work on him. Things like Kirby's Star Rod, Rainbow Sword, and Love-Love Stick would be able to pierce his defenses, and Meta Knight's magical fire-alien crafted blade Galaxia would be a better tool than the Master Sword on account of its similar backstory and feel to Link's blade. It meets the criteria established as the weakness.
Now then, let's say that we've got some sort of character who has won many a fight against a mage because of his ability to resist spells targeted at him with ease. Fireballs explode harmlessly around him, and he's still standing after the dust from a polymorph spell clears. I would say that this character's magical resistances would be able to repeatedly ward off Killing Curses from Harry Potter, Majin Buu's Candy Beam, or Kamek's attempts to turn his weaponry into flip-flops in the Mario-verse. They're all still mages trying to slam him with spells, and he is walking anti-magic, so it makes sense to me. I would say that he would not, however, enjoy a Kamehameha or a fire bender's attacks nearly so much, as those are ki, not magic.
It's all about pattern recognition.
An explanation, courtesy of Webcomic El Goonish Shive.