Well, if you want stand-alone + sci-fi, try "the Dark Side of the Sun".

Otherwise, you can pick up any first book from one of the Discworld story arks. Personally, I'd go with "Wyrd Sisters" (witches story ark) and the City Watch story ark. Although the first book in that series is "Guards! Guards!", I'd recommend starting with the Second book, "Men at Arms", which is more representative of the rest of the series, and just more fun AFAIC.

Agree, with the city watch arc as the discworld introduction. I'd even go so far as to say start with nightwatch and then go back to the beginning.

Personally I found the witches arc the slowest to get in to. It's too long ago to remember why I found that, but they sat unfinished. I've read them all several times now, and enjoy them, but only after I'd thoroughly got into the rest of Discworld.

The City Watch sub-series is my favourite with the Death arc a close second. laurentl already made recommendation on City Watch, if you want to try the Death arc Mort is the first.