Good question. Basically, you can start with any novel.
The first novel, The Colour of Magic, is a nice start because it introduces you to the Discworld as if you were a tourist. You’d probably have to read The Light Fantastic as well, though, because the second Discworld novel takes up the plot of the first one.
My personal favourites are currently Night Watch and Hogfather. They exemplify the Discworld character best, in my opinion, and are both funny and serious.
As a general rule of thumb, the Death novels (Mort, Reaper Man, Hogfather) are the more philosophical ones, while the City Watch novels (Guards! Guards!, Men At Arms, Night Watch) are rather sociological and Charles-Dickens-like. If you want fun and plain fantasy, try the Witches (Wyrd Sisters, Witches Abroad, Lords and Ladies).
Long story short: Start with The Colour of Magic for a fantasy parody or with Night Watch if you want something a bit more serious and multi-layered.
I hope I didn’t confuse you too much with all that babbling!