1) You can do an in-place upgrade from 5.2.9 to 6,5, no uninstall is necessary, but a reboot will be required to get the newer kernel mode IPS driver to load. You can wait, but it will use the older IPS driver until the next reboot.
2) 6.x managers can manage any agent that is 5.2.x or newer. However, 5.2.x agents can only use 5.2.x policies, and the 5.x policies cannot be upgraded to 6x policies automatically - they need to be re-created.
I don't have a best practice guide, but see the 6.5 doc "Planning and Deployment Guide" that ships with the product.