I see multiple websites off one codebase as one of the holy grails of using DNN, but there are criteria for making the leap.

Your backup, restore, testing, and all other workflow procedures need to be absolutely bulletproof before you make the move. The efficiency gained is met with an equally increasing risk factor and you have to ensure that you mitigate the latter with an equal increase in the precision of your procedures and reliability of your resources.

It's fabulously efficient to be able to add a new function to 500 sites all in one go, but also a nightmare if you stuff it up and have 500 clients calling for your head. My mind has boggled at some of the haphazard multi-portal DNN installations I've visited... one of them had hundreds of dead portals containing only messages such as "Visit us at our new vbulletin/mambo/joomla/whatever site here..."

I recommend it for pedantic perfectionists, but would advise sloppy people to stick with one portal at a time. 

Them's my two Cents.

Rob