I have the same situation, but with my programs on a C: SSD drive and my runtimes in a mirrored D: internal drive(s). I don't remember having any problems setting up or linking to my runtimes.
I suspect the change came because of Windows. To let Poser write to its main runtime without making your machine less secure, the library cannot be in the Program Files folder. One of the most frequent questions I saw from newbies since Win 7 had to do with permissions and changes to the main runtime in the Program Files folder.
The UI issue is a PITA. I like the interface layout well enough, but I wish it was built in something more flexible, accessible, and standard. If you ever take screenshots, you can actually see how certain things are placed by hand and not actually aligned, because the interface doesn't work on a grid. That said, I know that they've done a lot to use an old, specialized system in as structured and standard a way as possible. Recreating the whole interface in a new system would be a huge undertaking, and I'm not sure it would have much of a payoff for them.
