Joel & Ellie

honorable mention to Sonic + Tails, and R&C

Joel and Ellie by a pretty wide margin because the rest don't even count as characters due to their non-existent development (except for Luigi, that wrathful, cowardly, self-centered, narcoleptic is easily Nintendo's best character).

Ratchet & Clank

Donkey and Diddy Kong from the first DKC were a perfect team in my opinion.

Sonic and Tails. Luigi sometimes just feels like a clone of Mario..

Sheppard and Co.

Spyro and Cynder from the Legend of Spyro series.

I know you're asking for duos but I'd like to shout out to the NPC's that assist my character and make my experience awesome. Shout out to:

Pikmin: You guys are the real star of the game....which is why it's named after you, I guess.

Delta Squad: Made it possible for badass Marcus Fenix to get the job done. You too, Carmines.

Rebecca Chambers/Billy Coen: When I was using one, the other pulled their own weight.

The Freedom Fighters from Freedom Fighters: We did it for 'Merica! In later stages, I didn't even have to fire a bullet. I'd telly you guys what to do and you got the job done. Good job, guys.

Now that's just rude. Luigi is clearly taller than Mario.

I don't see it.