We are talking about a hero and a sidekick here. These are the two you think have gone through the worst of time and prevailed. They are the two who kick ass, but also able to make you feel with them when everything is against them. Video games are filled with these Duo's, but who have a certain place in your heart? (trios are welcome too)
For me its Jack and Daxter, they can be funny while also showing great emotions. Talking design and personality they are almost perfect. Jack, with his smooth hair and sweet moves, makes it a true pleasure to play. He is deep, dark but somehow always manage to be a hero anyway. Daxter being his almost opposite, being the comic relief of the two this guy is loudmouthed and makes sure his opinions always are voiced. Being a hero is something he would avoid if able since hed rather just relax and get comfortable so he may be somewhat of a coward but as Jacks friend he is always there (on his shoulder).
Oh... they kick ass too.

Jackie Estacado and The Darkness. Mafia Hitman and TOTAL EVIL POWERZ PWNER = insane fun and voices. THe guy who did the voice for the Darkness was his voice. IN other words, no post voice processing.
Daxter is a dumbass, especially after he was sucked into the sewer line and spat out.
Oh, and when he got his own decent game that turned out to be a trainer for bug exterminators...that ryhmed.

Minsc and Boo.
/thread

Hmm... it's on the tip of my tongue... something about a duo of Italian plumbers... ;)

Pfft, can easily match that with several equal or better ones
The Nameless One & Morte
Manuel Calavera & Glottis
George Stobart & Nico Collard
Guybrush Threepwood & Elaine Marley (might not count since elaine was an objective rather than a sidekick half the time)
Jeanette & Therese Voerman (another possible cheat)
Sam & Max
Marcus Fenix Dominic Santiago
Wallace & Gromit
Lara Croft & her boobies

Doomguy and super shotgun. I declare victory. But lets continue regardless.
Jade and Pey'j
...
Can't think of anyone else that hasn't been mentioned.
EDIT:
Fixed BG&E name.

WIN!

Max Payne and Vinnie Gognitti.

Sam and Max
/thread

Screw them. Giana & Maria can kick their ass any day of the week ;-p

If anyone says Ratchet and Clank... They are not a good pair. Clank is really nothing more than a smart arsed backpack.
Anyway:
Sam and Max
/thread

But that's a trio... :o

ratchet and clank :p
no , i'd say the brothers from redneck rampage
and billy and ray from call of juarez

Jade and Pey'j, unless we're thinking of different duos