Magento

We have worked extensively with Magento for over 4 years now. We have never worked with a more sophisticated open-source web application.

Some of the key benefits and features of Magento are:

Community. It's big, it's sophisticated, and it's growing. Fast.

Support. adequate for the free Community Edition (CE), but as eBay bought Magento as the eCommerce platform of choice for their forthcoming X.commerce suite. That tells you a lot about the application.

Architecture. Although it may seem over-architected (as Rob Smith mentioned), never before have I worked with a system powerful enough to meet my every need. Magento is built to scale from 1 to a million, avoiding common pitfalls for developers. Code re-use, maintainability, debugging, support, etc. are all huge, expensive problems that eCommerce solutions providers must tackle. Magento makes them all a breeze.

Out-of-the-box feature set. Magento handles concepts properly and in an organised manner. Stock Magento comes with Simple, Configurable, Grouped, Bundled, Virtual and Digital Products. You can use it to sell amusement park tickets and digital music at the same time, without any extensions.

Extensions. You knew it was coming. If Magento doesn't already do it, go find someone else who already has. 90% chance it's already available, and most of these extensions are dirt cheap (unless you're looking for integration with, say, an ERP).