Updating .NET framework

Great question. Last year our compliance group brought this to me. Therefore, I started researching on how to approach an upgrade for about 5000 servers. During this investigation, a strange thing happened. I learned a lot more about .NET than I wanted too :)

Back on topic though. The way I approached this was to focus on the versions of .NET 4 that were out of support. 4.0, 4.5 and 4.5.1. We have been upgrading to 4.5.2. We have stayed from the 3.5 sp1 stack (3.5, 2.0). This has been highly successfully effort with no issues really. The .NET 4xxx stack is where quirking has been leveraged which has made the upgrade process very solid. I hihgly recommend heading on over to the .NET blog for more info. Very useful blog.  

-- https://blogs.msdn.microsoft.com/dotnet/2015/12/09/support-ending-for-the-net-framework-4-4-5-and-4-5-1/

A couple of things to note. Once you upgrade to 4.5.2 or higher, you will then need to patch it because you'll be missing security updates. My recommendation would be to stay away from he Quality updates at this point so you are not adding complexity to the upgrade process. Upgrade, then apply security patches. Circle back around with the Quality updats once you are comfortable. 

Good luck!