Just to give people following this thread a little update: Brian's issue was, in fact, a window blocking the physical mouse click. A "Force Quit" dialog was still open and it's the kind of thing that will fool you into thinking it's not there unless you specifically bring up the Window Chooser, select the item and close the window. Same thing applies to the Notification center and some other system dialogs like those asking whether you wish to run updates, install other software, etc. Mystery solved.
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