I've not read a huge number of Discworld books yet - became a fan of Pratchett through Good Omens and my rabid Neil Gaiman obsession.
I'm reading out of order, but so far, my favourites have been Monstrous Regiment and The Truth. I like how the crazy humour of the earlier books (shopping trolleys and snowglobes in Reaper Man - brilliant) are tempered by a little more seriousness in these two.
Also love the books featuring Death, and the Witches so far (Wyrd Sisters is much funnier with some knowledge of Macbeth), and just starting on the books featuring Vimes now. I'm at the beginning of Guards! Guards! and just want to hug him and give him a warm bath, but maybe that's because I read MR first.
Worst would have to be The Light Fantastic, only because I couldn't bring myself to finish it. A few too many scantily clad women of myth in those first two books.
Also, I have a friend who might be doing a stage adaptation of Lords and Ladies, sponsored by a Shakespeare Society, if copywriteness allows. So yay!