I'm boring and a traditionalist and it's terrible but I'd start at the Colour of Magic and then go on sequentially, in the order they were written. I've done some "skipping about" over the last few books, and I'm finding it really difficult to work out in my head where in the sequence they fit. I know that the stories are, to some extent, separate, but the threads are so entangled that I feel that reading them in order would help with the knowledge of the Discworld - especially CoM/Light Fantastic/Mort where so much of the basic background and terminology is introduced.