I'm a little surprised, as I build a framework build and install it, create a venv from that, then run the tests in that (on Leopard - I have no access to a more recent OS X version). All tests used to pass, I now get occasional failures in test_tcl (hard to reproduce) but that's about it.
Hmm, that's odd indeed. Ned Deily reported that in his case sys.prefix was not set correctly in the virtual environment. I think he was on Snow Leopard? Possibly even Lion? You may want to connect directly with him to explore this further; I have no OS X of any version so can't be much use.