It'd probably be quite a barrier to signup, although I guess a 'mailto:register@example.com?subject=signup-for-$uniqid' link might solve some of the hassle.

The major issue I can see with it is that many people might like to use a email alias to signup (I prefer to use shabble+servicename@ for services which aren't too broken to accept a +) which isn't the same as their configured sender.

You'd have to be comfortable losing a LOT of otherwise perfectly good sign ups.

much better to do it the other way - allow your users to fill out their email address _once_, generate a confirmation link and mail it to them.

If they really want to service, they'll click the link.