Until recently, the primary go-to source for help was Aaron Stebner's WebLog on MSDN Blogs at Unified .NET Framework Troubleshooting Guide. I have also provided the recommendation to install .NET Framework security updates, with a shutdown/restart and separately from other security updates.
Troubleshooting .NET Framework problems may be near an end with the release by Microsoft of the Microsoft .NET Framework Repair Tool. As described in Microsoft KB Article 2698555,
"The tool may make one or more of several possible changes to the installed product. For example, it may correct the state of Windows Installer on the computer, reset the DACLs on certain folders, or resolve some issues that are related to invalid or corrupted update registration.
The tool follows a four-step process:
- Try to troubleshoot the issue.
- Apply the fixes (with user consent).
- Try to repair the .NET Framework 4.
- Collect logs (with user consent)."