Worth noting- the /fstacks thing is helpful because whatever this issue is, it’s related to layers. My guess would be that in creating the new (old, if you use Bartender4) functionality of letting us hover-set hotkeys, they may have added or removed “stacks” or layers. Different add-ons use these layers in different ways, and typing /fstacks makes things on layers visible. If then you click on whatever’s highlighted green in the middle of your screen, it should tell you what the green thing IS, so you’ll know what needs to be disabled for now. You can then type /fstacks again, to toggle this layer-visiblity off.
It appears Atlas Loot is/was causing the problem for me
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Disable out of date addons. I disabled Atlas Loot and it worked again. I was having this issue, mouse buttons barely working intermittently. Buttons work just fine in menus but not in game. Mouse seems irrelevant as I have tried several and all have the same problem.
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Have a +1 love heart and my thanks. Exactly what I needed!
Thank you! This solved my problem.
I was noticing it was as if there was an invisible box in the middle of my screen where my mouse clicks wouldn’t work!
I am getting the same problem where there is a tiny spot in the middle of my screen where mouse click interactions do not work some of the time. Mouse binds also do not work if cursor is sitting on top of action bars. I disabled all addons and refreshed my cache folders. I do not and have never used Atlasloot which seems to be the main culprit for a lot of players here.
was Atlas that was causing the problem for me
Strangely, AtlasLoot worked for me, but it was BeanCounter and Bartender4 that were the culprits. And then I quit for a while, and now my characters have all disappeared again. I just can’t win. At this rate I won’t be able to play until after the expansion drops.
I was having the same issue. I saw one of the replies to this post saying it had to do with the atlas loot mod. I deleted my mod and the mouse worked fine when I logged back in. Not sure if that is the fix for it, but it is working now.
After the AtlasLoot fix, I knew there was still something that felt off. This is absolutely what it is but haven’t seen anyone else post about it…
Having the exact same issue and it’s infuriating to play like this.
I was having problems looting things and interacting with NPCs. I found a new option under Interface /Controls “Open loot windows at mouse” Unchecked that and now my mouse works perfectly.
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Tried that…no change here 
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That’s been around for a while, but I don’t have that checked anyway.
I now have a SECOND character this issue is happening with… 
The only thing I can connect it to is that both these characters were logged in for the first time after the patch in a zone which had a current assault happening. (One was Zuldazar and the other Tiragarde Sound.)
EDIT:
So I tried the /fstack thing and there is a DEFINITE difference between my two characters experiencing the problem and my characters which do NOT have the problem. But I don’t understand what it means. Here is the difference I’m seeing:
Characters WITH the problem:
~https://ibb.co/cbVJM5f
Characters WITHOUT the problem:
~https://ibb.co/T1dzFkL
The difference seems to be a frame in the middle of the screen exactly corresponding to the area of the screen where the mouse is unresponsive which has the notation of “–><1> UIParent.24c5390ea70” listed under “High”. On my characters without the problem, there is nothing on the screen with a listing under “High” when I mouse over everything.
Can anyone help explain to me what this is?
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Same, I’m using a Logitech g602
I found a weird workaround. Installed Bartender and that seemed to solve the issue where mouse binds don’t work if hovering over action bars. That’s right, Blizz, I INSTALLED an addon to fix a UI problem…
Nothing changed for me at all. I even removed all keybindings and it’s intermittent, only not registering mouse functions seemingly whenever it feels like it. I have a Razer Naga Epic.
Also this is happening on all of my toons, regardless of layout, level, area, etc.
If your having issues with your mouse not being able to click on objectives or show tooltips then this is almost 100% an issue with your add-ons. More specifically the AtlasLoot Enhanced add-on. I had this same problem no matter what mouse i used and the only thing that fixed this was disabling AtlasLoot.
It’s not JUST AtlasLoot though. I had trouble until I disabled a number of addons as well, but in my case, I suspect it was RareShare.
Make sure your add-ons are up to date as well. If not they may be cause issues as well. When in doubt disable add-ons one by one until something changes.