"Reaper Man" is a good standalone. I'm also fond of "Small Gods," which is just a one-shot. No other books stem off of it, in other words.
There are "series" of books within the Discworld that happen chronologically to the same characters, but not like actual series; if you read the books in the order of publication, you'll jump from character set to character set but you won't miss any significant events in anyone's stories. Otherwise, the major threads are:
Death and Susan:
Mort
Reaper Man
Soul Music
Hogfather
Thief of Time
The Witches of Lancre:
Equal Rites (sort of)
Wyrd Sisters
Witches Abroad
Lords and Ladies
Maskerade
Carpe Jugulum
(These sort of fade into the Tiffany Aching books, which are also awesome.)
The Wee Free Men
A Hat Full of Sky
Wintersmith
I Shall Wear Midnight
The Night Watch series:
Guards! Guards!
Men at Arms
Feet of Clay
Jingo
The Fifth Elephant
Night Watch
Monstrous Regiment (sort of)
Thud!
The Rincewind books, which kicked off the series:
The Colour of Magic
The Light Fantastic
Sourcery
Faust Eric
Interesting Times
The Last Continent
Everything else is mostly a one-shot. Pyramids, Moving Pictures, and so on. They involve the same characters and many of the same set pieces, and sometimes you'll see a reference to other events (which can be confusing if you don't read in straight chronological order but never impacts the story overmuch.) For instance, Death appears in virtually every novel in at least a cameo, and the Patrician generally gets involved whenever Ankh-Morpork is a major setting, but this is more a factor of the persistent world effect than a real chronology issue.
Wikipedia has a handy list of all the novels in the order they were written, if that helps.