Monstrous Regiment is the only non-Tiffany Aching Discworld novel I read and thought, “Well I’m never reading that again”, although there are some others I have not yet re-read.
Night Watch deserves every bit of praise it has received here. A masterpiece. So many deep emotional impacts; hits ya right in the wossnames, every time.
Wee Free Men is my most recommended, because it features an excellent protagonist, an excellent story, an excellent message, and it doesn’t bog down its own lore or get lost in jokes. That said, my favorite Aching book is probably Midnight, and that one is in the running for my favorite overall.
My weird personal gem is Pyramids, which I rarely see on lists of best OR worst, living in the forgotten middle. Can’t tell you why I like it, but I’ve read it twice and both times walked away thinking, “why isn’t this better regarded?”
Men at Arms was the first I read (random grab at a local bookstore) and will always have a special place for me.
Speaking in terms of the subseries, I always felt that the Watch stories were the most gripping but the Witches were both the funniest and the most stirring.
Picking a favorite, it seems, is a difficult thing.
I wanna say Wyrd Sisters because I got that one signed. I’m going to have to reread them all though to be sure. Not a problem.
That wouldn’t help me any. 
Have to agree with Mr. Shine about Monstrous Regiment. I knew the twist from the title, and the story didn’t hold the slightest bit of interest for me. About the only thing that was worth anything was the Abominations Unto Nuggan, which were hilarious and which I have nicked for my own use here and IRL.
I agree; I think it’s the one where he really hit his stride as a writer. I think it’s less regarded because it’s more of a stand-alone and takes place for the most part outside Ankh-Morpork with no characters who will recur later, but yeah, well worth rediscovering. And the rooftop sequence during the Assassin Exam is a minor gem.
I really love Thief of Time. It’s the one I re-read the most, to savor the bon mots, the humor, and the philosophical ramifications of its view of reality.
I admit that City Watch is probably the most literate of PTerry’s works, but while I love it too, it doesn’t give me the Wow factor that ToT does.
But that’s just me.
PSST! Night Watch, while you can still edit.
Meh, I’m slow and getting senile and don’t give a damn about it anymore either. 
I haven’t read them all, but I’d say probably Lords and Ladies.
I love 'em all (well, maybe not the first two so much), but as a long-time fan of the Phantom of the Opera, it has to be Maskerade.
Carpe Jugulum isn’t my favorite, but it’s grown on me quite a bit. Like, when it came out a common if not consensus view on AFP was that it was Lords and Ladies only not as good, but I’ve started to see its charms.
Small Gods may be my favorite, but it was the first one I read and I may be biased.
Night Watch is my absolute favourite, but there are so many that I love nearly as much - The Wee Free Men, The Last Continent (the first that made me actually laugh aloud), Hogfather, Carpe Jugulum… and an honourable mention to Where’s My Cow which I reread to the kids the other night and we all had such fun with it.
No one has yet mentioned The Last Hero? That’s another with a great mix of story, humor, and sentiment. I gave it to my mom when she was looking for books about aging.
The very first scene, of Pteppic loading himself up with all sorts of weaponry, then falling over because the extra weight, always gets a laugh from me. As does the great mathematician You Bastard.
I had listed Wee Free Men as one of my favorites in a post above, but realized that I had misremembered - I was thinking of A Hat Full Of Sky, because that’s when Sir Terry explained First Sight and Third Thoughts, and what exactly witches do.
And the philosophers of Ephebe. Didactylos is my favourite Pratchett name joke.
Ok. It’ll be a short list:
…
I mean, Eric is my least favourite, but it’s nowhere near a bad book.
I couldn’t possibly choose! I can maybe set up a list of about ten books that I like a bit more than the others but choosing “The One Favourite Discworld Book”? No chance at all!
Most of the books I immediately thought of when I read the thread title have already been mentioned: Night Watch, The Last Hero, Thief Of Time, Going Postal…
The one I haven’t seen named yet is “Thud”. For me “Thud” is a perfect example for what makes the Discworld books so special: the joke about Koom Valley is as old as the Discworld series. I think the first little throwaway line about a battle between the dwarves and the trolls, where both sides ambush the other, is in a footnote* in “The Colour Of Magic”.
The joke comes up a couple of times more in different books and it gets more and more serious until - some 30 books later - we finally get the whole story. And the most heartachingly beautiful conclusion possible.
Can I also include a book that’s not set on Discworld? Because for me “Nation” is one of the best things ever written by Terry Pratchett and no list of favourite works could be complete without it.
*Where else? 
I thought Snuff and Raising Steam were both extremely disappointing.
Whereas I have Snuff in my top 5.
My favorite is certainly Small Gods. No, wait, it’s Night Watch. Except Interesting Times is actually my favorite…I mean, The Wee Free Men. Yeah, that’s it–no, except it has to be Thief of Time that’s really my favorite. Um, just a sec, The Last Hero is the best. And Maskerade, and Soul Music, and Wyrd Sisters and Reaper Man, and…
Nope. Can’t do it. It’s like picking a favorite line or a favorite scene or a favorite joke–the man was awesome and a genius…there’s no way I can sort 'em.
Also, I have found that different media give a different perspective: Read Colour/Light, then watch the Colour of Magic movie, then listen to the audio books, then read the graphic novels…each one emphasizes different aspects, gives different insights, makes different jokes funnier. That’s artistry, my friends.
You are all wrong. Reaper Man is the best Discworld book.