I ran into the same problem, and none of the solutions worked for me, at least not on their own. I found one more thing that may have been crucial:
After configuring the project to build on the 3.5 framework, I noticed a build warning in Visual Studios output window: warning : The 'language' attribute in the AddIn element is invalid - The value 'CLR4.5' is invalid according to the project's target framework version - The value should be 'CLR'.
After changing the language attribute in Config.esriaddinx file to CLR, things worked again.
Oh, and one more thing: Initially the breakpoint looks invalid (the breakpoint will not currently be hit). Don't let that fool you, because as soon as the addin is loaded, e.g. by clicking on a button, the breakpoint will be valid.
My other configuration:
- Supported runtime: v2.0.50727
- Require source files to exactly match the original version: Checked
- ArcGIS: 10.3.1
- Visual Studio: 2013 Update 4