In order to run the current alphas (34.100 and up) a .NET 4.6 installation will be required. The setup.exe will already check for that.

For our dear developers using the vvvv-sdk a Visual Studio Community 2015 installation (which is free) should provide you with all the tools required, for those who prefer SharpDevelop 5.1 the .NET 4.6 targeting pack and the Microsoft Build Tools 2015 should get you up and running.

A nice overview of all the different .NET downloads can be found here.

For a list of changes in .NET 4.6 have a look here.