DotNetNuke (now just DNN) is a powerful and flexible .Net based open source web application framework. The project has it's roots back in 2003 so it's sufficiently mature, there is a large and active community around the project (both open source and commercial) and it has Microsoft's backing, so this is a product that is going to be around for a while.
DNN is remarkably easy to use, it's not even too difficult to install and configure. A single DNN installation can support many websites (portals) each with a different look and feel (skin). Full international capabilities are built in as is optional user registration and management as well as a host of other features. It is not natively a content management system (CMS) because it does not support workflow, but this functionality could be added through commercial extensions. The biggest weakness is probably the official documentation which is a little sporadic and dated, there are though a number of books available written by various core team members.
Without a doubt the strongest feature of DNN for me is the ease with which the product can be extended through custom .Net development (modules). Within this web site (www.rmjcs.com) the T/SQL Script module (which takes basic text T/SQL as it's input and outputs CSS tagged HTML for the syntax high-lighted effect) and the Site Map module (no manual maintenance necessary, the site map is built on the fly from current page info) were created and deployed with very little effort.