If you run a legitimate business/operation with 100k real recipients, then you should have some insights as to where efficiency is needed. Are you actually encountering problems? How often do you send out new mails? Are the problems in the open rate of your mail, in the delivery/bounce rate of your mail?

If you are looking to improve your code, I would use a templating system like Template or Mojolicious::Lite to move the HTML from your "cgi code" script into a file. Also, I would protect the mail.pl script with a username/password so that other people cannot use it to send mails without authentication.