One method, all though maybe not necessarily the most efficient, would be to copy your top/clicked image to a canvas and do a look up on it for the color value of the pixel where the user clicked. If the alpha value of that pixel is transparent, call the onclick of the underlying image (or just return false if the underlying image also gets the click event automatically, I'm not sure if it would or not). I'm not exactly sure how long such processing would take, though.
Update: I just implemented this method and there's no noticeable delay copying the image to the canvas and checking its pixel.