Are you talking about WPMU?
See http://core.trac.wordpress.org/ticket/10201 and the couple of related tickets on user functionality-related performance.
Your error log might reveal an out of memory problem. I honestly doubt it’s an easy one to fix, too.
It’s possible to create a plugin that basically overrides the WP users functionality, yes, in such a way that it users a roles table. This was done by Sam for BBPress. I’m not aware of any for WP, but porting Sam’s plugin to WP shouldn’t be too much work.
quick aside, too: if you need paid-for support to fine-tune this part of WP and others on your site, email sales at semiologic dot com.
It’s for a regular installation of WP.
I was going to start on a plugin but wanted to check if there was a fix available.
If you have an analysis why the page get’s blank this should be fixed in wordpress core. You have some facts, or some code/stubs/dumps for 400k+ users to test?