One of the problems that we see at my work, often on a newly created development box, is that you can launch ArcMap from the debugger, but can’t break and examine code and objects. The problem for this often lies in the ArcMap.exe.config file. You must allow for the proper version of the .NET runtime in the config file. Without it, the CLR won’t load the right runtime and debug symbols won’t align with the code you are running.
To fix this, edit the ArcMap.exe.config file, which is located at: C:\Program Files (x86)\ArcGIS\Desktop10.2\bin. This post is for ESRI’s ArcMap, but it applies globally to all Windows exes that utilize .NET framework assemblies.
To run/debug against the 4.0 .NET framwork, make sure that you have this line in the ArcMap.config.exe file and you will be good to go:
You can read more about this from Microsoft in these two articles: