While I like Muffy, I can't see her getting a spinoff. She's such a central character on the show, and unlike Buster-- who regularly goes on travels and therefore a travel show with new characters makes sense-- Muffy more or less stays in Elwood City and tends to hang around the main group of Arthur characters.

If anything, I'd like to see a spinoff involving the Frenskys (with Francine being more or less an ancillary character or not appearing at all). They've introduced so many members of Francine's family over the years, I could see it working.