I don't see where XF would make a vast difference if a lot of your calls are to MySQL. Sure, things can be tuned better ....but VB 3 was written by the same team!
I am not a inside tech person by any means, but MySQL and many apps which use it are probably not designed for extremely large sites - of course, large being relative! The kind of traffic you mention is probably experienced by only the top 100 forums in the world (if that!)
Your number of users online seems doable.......I think a lot of this depends on how the particular Server and CPU setup distributes tasks (threads?) to the CPU(s).
As an example, I am using an older forum and CMS on my site and just upgraded to a XEON mid-level server.....actually pretty low level. But my mid-sized and relatively inefficient forum and cms with 800,000 posts, 23K members and 700 members online at the same time.....generating 100,000 page views or more a day, is not even starting to hit a server load of 1. Being a 4 core CPU, I'd think the server would not start sweating until the load hit over 4 - my estimate (based on nothing at all) is that with about 1200 users at one time we'd hit that.
Now, let's say I had a more efficient forum SW (XF, etc.) and two servers (db and httpd) and each was pretty upscale - like dual Xeons each and 8G or 16G or RAM each......
It's hard for me to imagine that such a setup would not handle thousands of users online at one time....
However, I think we mere mortals deal with too many variables to actually say without testing
If I were going to try to scale up more than 2 or 3X current traffic, I would look hard at Amazon:
http://aws.amazon.com/rds/
It will be educational to see more real world experience as some of you move to XF.