Today, Visual Studio 2010 and .NET v4 were released. With this, Paint.NET v3.5.5 is moving to use .NET v4, as I already announced would happen back in January.
Please note that XP SP2 and Vista pre-SP1 ("RTM") are no longer supported.
Just to clarify, XP is still supported! However, you must have Service Pack 3 ("SP3") installed. For Vista, you must have SP1 or SP2 installed.
3.5.5 Beta build 3754
Product page: here