I've been doing a few tests on the matter and I've been trying to pinpoint the cause of the perceived "unresponsiveness". I think that I've found it. It is caused by the interaction with attack animations. If you cancel an attack animation with a spell, you will get the animation of the toon getting into casting position and the rune appearing, but the spell doesn't go off. Your client though thinks that it is casting so if you click again that skill, nothing happens. I will try to make a video of this.