I often experience clicks that get lost "in the void" meaning that the
actual xfce windows does not seem to receive them.
Typical example: I use firefox, and a noscript pop-up ("load
anonymously") with a button to click on: but I can't. What helps then,
is changing the virtual screen (go away) and coming back: after this,
the click arrives again at the destination window. Very annoying!
I noticed something like this but I think it’s usually triggered by something in dom0. Most notably I have a finicky power button and I get the reset/logout/shutdown dialog. When I hit escape to make it go away, I have to change virtual screens back and forth as you described.
There's a longstanding bug where certain types of windows sometimes can't be clicked until focus is removed from that window, then given back again. I usually alt+tab to another window, then back to the original window to fix this. I'm not sure if you're experiencing the same thing, but it sounds similar. Also, I'm not sure if this is the right issue for what I'm describing, but it seems to fit: