I've had a few people who use iCloud drive have problems with Runtimes (from 13, 14 and 15) on their Macs. All of the Macs affected have been running Sierra. I haven't heard of any problems with < Sierra, but then iCloud drive isn't as foisted upon users in those OSes as Sierra. Many users don't even know they ARE using iCloud drive.
If the Runtime folder is on their iCloud drive, upon launch the Runtime will give the "Data File cannot be found" error that is common when someone moves the Runtime app out of the same directory as the data file. Only in this case they are indeed still together.
Selecting the data file in the ensuing dialog results in same error dialog, again. Dragging data file onto the App icon, ditto.
If the user makes an Applications folder in their home folder (that is, on the hard drive of their Mac, locally), and moves the Runtime directory there, the Runtime will return the same error, but selecting the file in the next dialog will indeed launch the Runtime. (That's at least one way to launch! though not optimal).
However, included Extensions do not enable in the Runtime in the latter case.
I'm delivering the Runtimes in a zip file, if that makes any difference. Anyone else seeing similar?