Smushing two genres together can lead to bizarre consequences, odd situations, and occasionally if executed well a campaign of pure awesome. I can see a muppet movie/007 mashup being one of the awesome ones. After all, parodies of James Bond tend to do well and the Muppets are really good at the parody genre. Of course this depends on the GM having a good knowledge of both genres, whatever genres they are. The knowledge is essential in a mashup because you want to keep the distilled essence of both genres and know what to drop out as extra fluff that doesn't further the mashup. Dropping the wrong piece can lose the feel of either of the mashed genre. It's also important to mash the right genres. Some genres mash easier than others. Highly serious and highly silly genres mix less well than serious and serious or silly and silly. Horror tends not to go well with high fantasy ("What do you mean run from the vampire? I cast daylight and charge it!"). All in all, watch your step when mashing.