As Matt said since 2008, there are too much improvements/changes in RadControls, so that it is difficult to list them all. However, you can have a look at the release history
of the controls which provide a detailed information on the matter.
We highly recommend to always use the latest version of RadControls (currently this is version 2013.2.611). Regarding the version of .NET, currently we support .NET 3.5/4.0/4.5, depending on the operation system. For a detailed information, please refer to Supported Server-Side Frameworks
Regarding the issues that may arise after the upgrade, you can make a test with our trial version. Please feel free open a support ticket (during the trial period) or a forum thread, in case any questions related to RadControls occurs.
You can also find interesting our online demos
If you want to get updates on new releases, tips and tricks and sneak peeks at our product labs directly from the developers working on the RadControls for ASP.NET AJAX, subscribe to the blog feed