The Fallout games have always been big on humor, though in my opinion some installments (I'm looking at you, Fallout 2) went a bit overboard, with all too obvious pop-culture references or just plain pubescent foolery breaking the immersion. But at its best, Fallout manages to incorporate a healthy dose of humor in its universe, tongue-firmly-in-cheek probably being the way to go with a setting that features such silly things as talking animals, robot dogs and intelligent plants (but I think we all want to forget that part, even the devs don't consider it canon).
None of my players are familiar with Fallout (After the first session, consensus seems to be that the universe is a post apocalyptical wild west, with sheriffs, tribals and cattle ranches) so they'll probably be in for a bit of surprise when the weird hits the fan! The plan is to try and inject a little of that typical Fallout humor in my sessions. So far it has been limited to a Firefly reference which mostly went by unnoticed, but more zaniness is waiting for my players just beyond the horizon. :) Upcoming wackiness will include: A decrepit old Ghoul whose legs were nibbled off by coyotes during the night, a hold up by a cyberdog with a human brain implanted, and after listening to this hilarious radio skit from the '50s by Stan Freberg called "St George and the dragonet", I got an idea for a Wild Card NPC Joe St George, grizzled mutant and deathclaw hunter. More weirdness to follow, without a doubt. :)