Seems our IIS instance stops responding, giving requesters a 500 error, and only restarting IIS (or running iisreset from elevated command prompt) gets it going again.
Nothing else stops, and sadly there's nothing in any event log (application, system and IIS) that points to what may be happening. It's like IIS decides it wants a holiday and just doesn't answer.
Software versions are as follows:
OS: Windows 2008 R2 running as a vSphere guest VM with 8 vCPU and 8GB RAM (fully patched)
Web: IIS 7
DB: MySQL 5.1.63 for Win64
PHP: 5.3.13, CGI/FastCGI enabled
Any guesses what to look for? Other than this annoying behavior the site's working pretty well as advertised.