Have upgraded our test server (non-production) from ePO 3.6.1 to ePO 4.5. Due to it not supporting MSDE, I had to first do an upgrade to ePO 4.0, then switch ePO to use SQL Express 2005, remove MSDE and then finally upgrade to ePO 4.5. So far, it is working fine. We only have two clients attached to it running the older ePO agent 3.6.0.608. I am using this test upgrade as a way of learning the new features. It certainly is a lot easier to learn than 4.0. Kudo's to McAfee for improving the menu system.
I have until the end of the year to update the production server.