I am also having this exact same problem with the Enhanced Edition from GOG, running on a late 2013 iMac with MacOS Sierra.
I have tried enabling/disabling every single graphical setting (whether or not I thought it was related to my problem), enabled/disabled all of the various tweaks and options in the launcher, tried every UI or camera setting, alternated between fullscreen-windowed-fake fullscreen, and even changed resolutions. Nothing has helped in the slightest.
As the OP described, what is happening does not appear to be related to mouse lag or the clicking input itself. Every click is being registered. What is apparently happening is that the cursor is clicking THROUGH the UI windows. Lets say, for example, that I open my character screen and click on the Abilities tab, which overlays the equipped gear tab. When I drag the cursor over any of the ability buttons, as it moves the buttons beneath it rapidly flicker on and off; if I click the mouse while the button beneath is highlighted, everything works as expected. However, if I click when the button is not highlighted then the click is actually registered on the tab BENEATH the abilities tab, which results in clicking on my equipment instead, even though I cannot see it.
Likewise, if I select a healing skill from my quickbar and try to apply it to one of my characters by clicking their portraits, half of the time the cursor will actually click THROUGH their portraits to the ground beneath.
In either case, getting the cursor to highlight the desired sections of the UI can be very frustrating as you have to keep moving it around trying to get it to highlight the desired part. This happens in every section of the UI where part of the interface is overlaid on top of another. If this were a real time game, it would be unplayable. As it is, it is merely aggravating, but it enough so that I might quit playing.
There must be a solution to this.
