Rach's Reading Club

I have read quite a few of them, but not all. I'm planning on completing the series this year. So you'll probably see more Pratchett reviews.

There are benefits to reading them in order, because of the recurring characters and their story lines. The downside to that is that it took Pratchett a while to properly hit his stride. Even Pratchett himself recommends against beginning with the first book. Depending on your tastes, some good starting points are:

Mort, in which Death takes on an apprentice.
Guards, Guards!, which is the beginning of the books about the Watch (the police force).
Small Gods, which is more of a stand-alone novel about faith, religion, politics and philosophy.
Equal Rites - this begins the books about the witches. It's only the third book in the series and the witches do develop more later on, but it's still pretty good.

Hope that helps!