I'm not exactly wise, but anyway: what makes your application slow is probably tightly related to the cause of profilers deaths. I'd try to narrow the problem down as much as possible, to isolate the module / set of modules that cause trouble. Try commenting out, e.g. with POD. Is there some heavy lifting in an inner loop somewhere?
Do you have tests for the project spesific modules? They should probably be prime suspects... If you make simple tests to check their sanity, you can also to profile these tests in isolation.