Problem
After In-place upgrading from Windows Server 2008 R2 to Windows Server 2012 R2 (not a good idea in a production environment) and activating the new Windows Server Updates Services Role, I encountered several errors. The machine also had the System Center Configuration Manager 2012 R2 installed.
The post-installation task ended with the error Failed to start and configure the WSUS service.

A manual start did not work either (Error 193: 0xc1):

Reason
CCMSetup (SCCM) created a file called Program in the root folder and the WSUS Application Pool ran under the wrong .NET CLR Version.

Solution
Delete or rename Program file and change the .NET CLR Version from .NET 2 to .NET 4.

After an IISReset restart, the Post-installation tasks of WSUS:
