Mortal Kombat vs. DC Universe
Pitting the most brutal group of fighters this side of the Roman empire against the Justice League hardly seems fair, until you consider that the Justice League have superpowers. When it comes down to pure ruthlessness versus flying and shit, flying usually wins.
That, plus Mortal Kombat's infamous savagery was considerably toned down for MK vs. DC Universe, presumably so Scorpion and Johnny Cage and the like wouldn't show up their comic book opponents too much. Disappointment about not getting to watch Superman rip someone's spine out notwithstanding, though, it's a hell of a great mash-up.