I'd recommend x-cart (
www.x-cart.com). Very mature product, LOTS of stores using it, and tons of add-ons, including a pay-per-download module.
Zencart and OSCommerce are also good, but from what I've heard from our programmer, both are more difficult to customize because of the way the code was developed.
Also, the x-cart people will do customizations for you if it doesn't have quite what you want out of the box, and they're generally pretty inexpensive. We've been using it for about 3 years now, and I know sites doing 10 or 20 times what we do in sales that use it without a hitch.