I've noticed that, very randomly, I'll lose the ability to run my project by either pressing F5 or clicking the big "Run Layout" button in the top ribbon. Strangely I can still run the project by right clicking on the root node in the solution explorer and run from there:
Closing C2 down does not seem to help, nor does selecting a different run browser in the settings.
Windows 7, 64bit
Construct 2 version: Release 101, 64 bit
Last browser used before setting broke: Chrome 21