One thing that is coming to me from the top is the ability to respond to an email notification to approve or deny it. This behavior would be similar to many mailing lists were you hit reply to approve the subscription or send to a different email address to deny. How would I do this in an Exchange and ASP.NET environment? Are there any examples of someone else doing this?
I currently do this via a link in the email, but if they are on their phones or out of the office, they can't access the intranet application.
You'll have to monitor the incoming mailbox and respond to keywords in the email (subject or body). If you want to perform multiple actions (ie approve or deny), the simplest way is to create mailto links in the email body. That way, the mailto links will include your keywords (approve, deny, whatever) in the subject line when clicked.