I finally found a way to do good vacation auto-replies with Mail. This hint is for those folks who can't set up vacation replies on their mail servers and have to rely on their email client.
I was frustrated by the fact that Mail would reply every time I received a message. I wanted a solution that would reply only once to each person. I found this script on MacScripter.com, and it's so simple that I'm surprised I hadn't seen it before. Basically, it adds the sender to a group called Vacation, and you set up a rule to only reply to people who are not in the Vacation group. So once the person gets a first vacation message, they won't get any others.
[kirkmc adds: My first thought was this: do people really leave their Macs on when they are on vacation, just to send auto-reply messages telling people they are on vacation. Then, chatting with Rob (in between his morning massage and the drink-with-the-little-umbrella, he said he never turns off his Internet connection, and always leaves at least one Mac on when on vacation. I thought how much power that wastes... Hence this poll.]
Mac OS X Hints
http://hints.macworld.com/article.php?story=20071003074333429