Have you visited one of those sites that has an annoying advertising pop-up when you mouse over a link? While I find those somewhat annoying, at least they're usually well marked (via double underlines), so you can easily avoid them. Worse, to me, are hyperlinks that appear normal, yet pop up useless information on mouseover, without any warning whatsoever.
True, I have one such link here, for the "Why is this required?" link in the spam blocker. However, that pop-up contains useful information, and it's located on the right side of the page, where it's unlikely to be accidentally activated. So I think it's OK :).
The ones I find really irritating are the Snap Preview Anywhere pop-ups, which show a small thumbnail of the page you're about to visit when you mouse over a link--talk about a complete waste of bandwidth! I rant about these (and provide some suggestions to actually make them useful) in more detail in this Macworld Editor's Notes blog.