I'd try to design a line inspired by classic TV shows, with top-quality leather (like the ones Hyacinth listed) and solid (or hollow, if weight requires) hardware that's made of the metal it looks like. If it looks like brass, it'll be brass, by golly! The line would not necessarily be graphics based, more like prevalent motifs in the genre would influence the designs. Graphics pieces will be the only pieces to use saffiano/ crossgrain/ or similar. I'd price it so that most people who wanted it could afford it, since it'll be so awesome everyone will want at least one thing.
Westerns: Horse-inspired motifs would be appropriate, maybe a few graphics pieces of horses running free or with cowboys or stage coaches. Although a gun owner myself, I don't like to see them on bags (and there's all ready mall kiosks and flea markets full of them anyway), so no gun graphics, or anything disrespectful to Native Americans.
Sci-fi: Robot and spaceship-inspired designs, with a few themed pieces (TARDIS hangtag case, anyone?). And you can even fit dinosaurs into this branch, thanks to shows like Land of the Lost!
Horror: Finally, campy horror, ala The Adams Family, The Munsters (Dragula: the bag!), Dark Shadows, etc. Expect lots of black suede, dark velvets and satins, gunmetal hardware, and maybe even spider-web patterned lace on this line.
Designing our own lines would be a lot of fun...
You had me at TARDIS.
