I can see what you mean. Still, Rincewind was an Ankh-Morporkian at heart - even though some of the stories didn't take place in AM for most of the storyline-time- and even the witches had their guest appearances there. I think that it is just the setting that evolved more than any other Discworld setting. (Maybe it's just a typical trait for places like Lancre to remain pretty much the same at heart.)
One book that tried a totally new setting and, partly, tone, was Monstrous Regiment, and that left many fans bewildered. (I thought it was good, but often found myself in the minority there.)