Well, I solved the problem, but it was really odd.
I found a second OpusFSI folder inside of the C:\OpusFSI one. It appeared to have a complete program. I opened FSIServer from there, was able to change to E:\FSX. I then closed that program and re-opened FSIServer in C:\OpusFSI. It was properly changed there, also, to E:\FSX! I then deleted the inner folder and everything appears to be functioning correctly now.
I have no idea how that happened, unless at some point I failed to uninstall before installing a new update somewhere along the way.
In any case, problem solved.