I think Kevin Smith would be an excellent director for this kind of movie. He likes the story told as if you're there, with the same two shots, and I think that'd be a perfect way to film a QC movie. Also, the humor is right up his alley.
I definitely could see Kevin Smith doing this, but I think Edgar Wright would be interesting even though he usually does more high-concept films. Wrights seems to have perfected portraying the beta-male and is fearless with his humor.
Edit2: The more I think about it, the more Winona Ryder would be a good Dora.
Except for the fact that she's a bit too old.
I think it would be better to pick more from TV actors... They're less known (which allows people to concentrate on the character, not the actor) but still have proven they have the chops for their roles:
Marten: Lee Pace
Faye: Thora Birch
Dora: Amy Adams (I will defend this choice if necessary)
Raven: Allyson Hannigan (she would be able to pull of the comedic elements of Raven's character)
Hannelore: Anna Friel (I'm on a "Pushing Daisies" binge)
Steve: Bret Harrison
Voice of Pintsize: Morgan Freeman