I've had this issue for awhile with VLC, but i just ignored it and used keyboard shortcuts but it's finally gotten on my nerves.
I've tried uninstalling, deleting the cache, reinstalling, all the basic trouble shooting steps.
The issue happens as soon as I start VLC, and oddly the right mouse button works fine. The only way I can make the menu buttons/playback buttons on the bottom respond are if I repeatedly right click and then press the left mouse button like a maniac on whatever option i'm trying to use.
The skinned version works ... Kinda. The play pause button will work fine, but anytime you try to access the regular menu (Like Menu Interface, Effects and Filters/ CTRL E) it becomes unresponsive again to the left mouse button.
It's just irritating and I can't figure out what the issue is. Really like the player, but other than very basic functionality in the skinned mode, it's essentially unusable and has been for awhile.
EDIT --
Running Windows 7 Ultimate 64 BIT
HD Radeon 7850 GPU.