I got bitten by this too. It was a site that was running just fine on PHP 5.2.x, but upgrading to 5.3.x broke it.
The specific symptoms are that include_once and require_once became no-op, and never included the subject file even if it was the first hit since the server started.
Disabling the APC cache resumed service in the WP admin. But that's hardly what you would term a fix. This led me to the apc.include_once_override configuration directive, which I turned off and service has resumed.
[ long rant about the steaming pile of annoyance that php 5.3 has been deleted ]