Hmm, tough one.
The Wizards of UU - I love the Rincewind books (bar Colour of Magic, but even that grew on me). But Unseen Academicals just drags the wizards waaaaaaaay down in my book.
The City Guard - Used to be my favourite, but they've become boring to me. Vimes has become everything he's ever hated, Carrot and Angua have lost any sense of humour and Nobby and Colon have been sidelined. Night Watch was just plain depressing.
The Witches - Love 'em. They're the best mix of humour and Terry's philisophical musings. Although I wish Magrat hadn't been sidelined in favour of boring Agnes.
Tiffany and the Nan Mac Feegle - Have only read the first two. Liked Wee Free Men, but thought Hat Full of Sky was only so-so.
Death & Co - Like these ones a lot too. My only real problem is that I find them the most samey (most of them are about Death taking a break from his duties), but hey if it ain't broke.
Moist Von Lipwig & Co - The Moist books strike me as perfectly mediocre. I don't dislike them like I do Night Watch and Unseen Academicals, but I could happily do without another one in the series. Love Small Gods and Pyramids (which is probably the one I've read most). Monstrous Regiment was decent. In the middle of reading Maurice for the first time and liking it so far.
So after a lot of waffle, The Witches win it for me with honourable mentions for Death and Rincewind.