I can only think of a couple examples when I've had spells not go off:

1) I just got slept. If you're fighting dodos, that may be the issue.

2) If you get hit by a mob while you're casting, there's a chance your spell will be interrupted and fail to cast.

3) The person on whom I tried to cast a spell got out of my range. But if you're soloing, that's not the problem.

4) If you click on the spell twice, the 2nd time cancels it. Sometimes I'll do this accidentally when I get too excited, and I want the spell to hurry up and cast.

Other than that, you may be having some UI delay issues. I'm not smart enough to be able to fix them, but the cause can be anything from running the game on a less than optimal computer, to internet connection issues, to server problems at SE. They've been working to improve UI lag, and it's much better than it was at launch. But they're still working on it.

It's also possible that I'm not sure exactly what you mean. You talked about switching between normal attacks and weapon skills/spells. But all you really do is press one button for normal attacks, and press a different button for weapon skills/auto attacks. You can't do both at the same time -- you have to wait until one move launches before you can do the next move -- but you don't really do anything to switch between the two. You just do one, and then do the other. So I apologize if I'm misunderstanding.

And by the way, Jinrya, your sig cracks me up.