I started by reading a few from around the middle in no particular order (starting with Soul Music), then bought the whole series and read them from the start. Reading them in the disorder is not much of a problem, even books that are part of the same series with the same characters have stories that stand up wholly on their own.

The series:

The Rincewind series: the first Discworld books are in it, but it's not the best; I'd recommend the others first. It's probably best to read the books in this series in order.

The Witches series: starts with Equal Rites, but starting with Wyrd Sisters is fine (Equal Rites is one of the early books, and not very heavily linked to the rest). I'd recommend reading Wyrd Sisters => Witches Abroad => Lords and Ladies etc. in order. Probably my favorite series.

The city watch series: starts with Guards! Guards!, I'd recommend reading them in order. A pretty good series.

The Death series: has several books, but they aren't heavily linked to one another, except maybe towards the end (I'd recommend reading Soul Music before Hogfather).

Standalone books: Small Gods, Moving Pictures, Pyramids ... not part of any series, but quite good.