The majority of our transient bugs on WordPress.com are probably related to APC opcode issues. We try to catch them and handle it gracefully, but it isn't always so easy.
In my experience, stable APC releases have been very stable, but beta APC can poop out pretty bad, even if the changelog doesn't indicate anything that might affect your application.
I've used stable APC + PHP + Apache releases to do some large things, so not sure why APC is an utter bomb in 2012.
My gut feeling tells me that your profiling is correct, however - any significant PHP application (that isn't written terribly inefficiently) will have its bottleneck in data access and not the parse/compile stage. There's very little point to speeding up by 250% a portion of your app that only accounts for 2% of execution time!
Maybe.