There's a bunch of pairings I really like but so little support for them. Spoilers beware! Here's my top three:
Seto Kaiba (Yu-Gi-Oh)/Hermione Granger (Harry Potter): This one can never ever happen in canon and everybody should know why. However, both are insanely smart people and I don't think they will ever settle with someone not as smart as them (Though I am a big fan of Ron/Hermione and Kaiba/Joey, oh well.)
Leon/Marian/Judas (Tales of Destiny): Threesome. This won't be able to happen except through time-travel and even then, it will be hard to pull this off without making OOC-ness. Plus, Leon and Judas are the same people and there must be some kind of rule against meeting with yourself in the past.
Marth/Sheeda (Fire Emblem: Shadow Dragon): Why don't I see more support for this one? It's practically canon! Marth and Sheeda barely show up in the Fire Emblem section of Fanfiction.net. I don't really want to wander through the warzone of Super Smash Bros. just to see Marth, even if he shows up more there than in his own section. Hopefully, more support will crop up with the DS remake soon.