I'm currently attempting to migrate from 4.6.9 on Windows 2003 to 5.3.1 on Windows 2012 R2. I've successfully run the Upgrade Compatibility tool on both the source and target, but when I run the 5.3.1 setup, it wants to perform a new install rather than an upgrade. I've run through the process a couple of times, and always get the same result.
Reboots did not solve the issue.
One thing I notice is that the Upgrade Compatibility tool places the ePolicy Orchestrator files under c:\program files, but the installer wants to install ePolicy Orchestrator to c:\program files (x86). Manually copying the files to the x86 location did not resolve the issue.
I found that I was not being patient enough when running the upgrade compatibility tool on the target. I had selected "close" when it was still on "extracting 100%" instead of waiting for the completion message.