Ran into a very strange situation today. Suddenly, Visual Studio 2015 RC's debug options broke and the F5 key would no longer start the project in debug mode. Even IISExpress had disappeared, only showing "Start", which generated this error when clicked: "The debugger cannot continue running the process. Unable to start debugging."
Another issue: The References folder was empty, even though .NET 4.5.1 and 5.0 were added earlier.
I tried a repair via the uninstall utility but issue was still there. Finally, I exported and reset all the settings in Visual Studio following this article. Lo and behold: the options were back and I could run the app in debug or Ctrl-F5 (non-debug mode). Why this happened all of a sudden today, I don't know. I wasn't changing any settings, just editing a C# file when Visual Studio suddenly stopped working.