All that is needed to clean the QVS memory is a QlikView Server service restart. If you have large qvw's, they will of course be loaded back into memory aftwards and this could take some extra time depending on file size and memory footprint.
Rebooting the server is up to you. I have seen people reboot every weekend, where others only do it if absolutely necessary, so it really depends on your environment and deployment scenarios.
When you cluster two or more servers, you always install one first, that I will call master, then using this server's QEMC set up and link to the other servers. This master server should be rebooted first, then in any particular order, the rest of clustered servers (slaves).