'Launching Main' has encountered a problem.An internal error occurred during "Launching Main".java.lang.NullPointerException
It turned out, that Flash Builder could not find the ASP.NET development server which I use to debug my flex-projects:
Flash Builder searches for C:\Windows\Microsoft.NET\Framework\v2.0.50727\WebDev.WebServer.exe, so I copied the files WebDev.WebServer20.exe and WebDev.WebServer20.exe.config from C:\Program Files (x86)\Common Files\microsoft shared\DevServer\10.0\ to C:\Windows\Microsoft.NET\Framework\v2.0.50727\ and renamed them to WebDev.WebServer.exe and WebDev.WebServer.exe.config.
Now everything runs fine again