Hi Jan,
I was upgrading from 16.5.0 to 16.5.5 and also going from 32-bit to 64-bit. I had the same problems as you after changing what I could in the PD Client (Options, etc.) interface. As Chris suggests, a complete uninstall of the old version, followed by a fresh install of the new one will work.
I chose to look into my existing installation and there were tons of Windows registry entries still pointing to the non-existent 32-bit installation directory (about 200 of them). There are now registry entries under an SAP folder and others under a Sybase folder. Some (many ??) of the Sybase ones are still in use because the installation had definitely changed those. I went through and changed them all to point to the new \Program Files\SAP\PowerDesigner 16 directory.
It all seems to be working now.