Diablo 3 nullifies any interaction requests every time the Diablo 3 window loses focus. The clearing is not called more than a few times per second, that means that you just have to send the click again once your character is standing at the thing you want to interact with.
You could also enable the background mode. Which allow the game to be fully functional even while running in the background. (like being able to hoover over a NPC while the window is not active), which is nothing more than.
(note these offsets are not the current)
Code:
0080EBEF - cc - int 3
0080EBF0 - a1 a0 d7 31 01 - mov eax,[mallocextension::`vftable'+11a53c]
0080EBF5 - c3 - ret
0080EBF6 - cc - int 3
changed to
Code:
0080EBEF - cc - int 3
0080EBF0 - b8 01 00 00 00 - mov eax,00000001
0080EBF5 - c3 - ret
0080EBF6 - cc - int 3