I spent 1 hr using an Admin account trying to get 6.3 to work under Vista Ultimate. I was using mIRC 6.21. After upgrading to 6.3 the application was using an mirc.ini and servers.ini that was the incorrect ones. It had no idea regarding my name and nics and there were servers that were not showing up in the servers list. After working on it for an hour, checking on the virtual store directory which was being used by 6.21 the ini files were correct. I uninstalled mIRC completely and deleted all traces of mIRC and its files from Vista. I may try to reinstall mIRC from scratch.
I got it installed and working so that it is using the global settings approach. Probably helped removing all of the mIRC. At least that way I knew I was dealing with a clean slate.