Moving programs from one drive to another

A little background: I am considering building a computer with a SSD for my OS and frequently used applications (such as games and startup apps) and a HDD for everything else.

So here's my question: If I ran out of room on the smaller SSD and had to move one of its programs to the larger HDD, would this be possible without a full reinstall of said program? My main concern is that registry keys or ini files will still point to the old location after the files are moved.

I don't see how that would be done without some ramifications that you wouldn't enjoy. It's not really a straightforward copy over. If you could clone or ghost your HD, then maybe it would work?