You want an honest opinion, I say it won't work - back in 2004 or early 2005, I tried to send to 4,500 users, and it was the most horrible experience I've encountered. While I think DNN is a first class product, emailing people on mass like that really does take some more infrastructure than DNN can handle.
I have my own email application (emailer) which really also is good for lists under 5,000 (XML is not a good tool in this space for using for tracking) Currently my emailer application is about 1/2 way being converted to a DNN product (yay) and it's looking good, but even so, there are things we need to do on the server to make deliver mail as it should.
I'm about to send close on 50,000 email to my user base but we use a third party sql based application for this, and I have a third party .net app that handles how the mail is sent - eg.. how many per second / minute and will handle bounces.
You'll also notice that dotnetnuke doesn't send from here, but they have lots of names and I don't know about you, but I got an email today from snowcovered as I've been missing the weekly releases, and noticed it's not being sent from dnn any more, so if you're looking at sending out perhaps bcc text based email - non personalised, quick to send out, it might be ok, but I'm not confident that DNN and mail sending is quite polished yet.
Having said that - DotNetNuke really is a fantastic product and for the most part, there aren't that many users in the majority of people's lists and it does it well, but there are limits, and I found over 4,000 was the killer for me.
Just my thoughts on the matter.
Nina Meiers