How to troubleshoot apps of which multiple instances can be launched

If it is a cache problem then I would suggest running AppleJack to clear caches and fix permissions.

It's a wonder of a tool. It would be my first step.

Found the answer for what's going on here, TL;DR:

Remove quarantine for the offending app, in my case:

sudo xattr -d -r -s com.apple.quarantine ~/Library/PreferencePanes/PTHPasteboard.prefPane

Apparently with 10.12 (Sierra) Apple has implemented something called "App Translocation" and is documented under the "What's New in OS X" -> "Security and Privacy Enhancements":

Starting in OS X v10.12, you can no longer provide external code or data alongside your code-signed app in a zip archive or unsigned disk image. An app distributed outside the Mac App Store runs from a randomized path when it is launched and so cannot access such external resources.

There is further explanation in "OS X Code Signing In Depth":

If using a disk image to ship an app, users should drag the app from the image to its desired installation location (usually /Applications) before launching it. This also applies to apps installed via ZIP or other archive formats or apps downloaded to the Downloads directory: ask the user to drag the app to /Applications and launch it from there.

This practice avoids an attack where a validly signed app launched from a disk image, ZIP archive, or ISO (CD/DVD) image can load malicious code or content from untrusted locations on the same image or archive. Starting with macOS Sierra, running a newly-downloaded app from a disk image, archive, or the Downloads directory will cause Gatekeeper to isolate that app at a unspecified read-only location in the filesystem. This will prevent the app from accessing code or content using relative paths.

See this for further information.

I really appreciate what the author of that article notes here:

Under what circumstances does App Translocation occur?

First, the app must have a com.apple.quarantine extended attribute. If you delete the quarantine xattr, then App Translocation does not occur, and the app will launch from where it was unarchived, like normal.

Second, the app must be opened by Launch Services. This usually means Finder, but it can also mean open from Terminal, for example. If you launch the app executable directly from bash, on the other hand, App Translocation does not occur.

Third, the app must not have been moved — by Finder. If you move the app, using Finder, from the app's original unarchived location to another folder, even a subfolder, e.g., ~/Downloads/Test/, then App Translocation does not occur.

However, if you move the app using mv from Terminal, then App Translocation will still occur. Normally you would move the app from ~/Downloads to /Applications, and that would cause the app to be launched from /Applications like normal, but the locations of the particular folders don't seem to matter.

The mere act of moving the app using Finder stops App Translocation from happening. Indeed, once you've moved the app once, it will no longer experience App Translocation again, even if you then move it back to ~/Downloads.