So what's large ?
In My Mind a large mailbox is anything to impractical for an OST, so anywhere above the 2GB mark, depending on hardware. The slower the hard drive - the smaller the OST becomes.
By deploying large mailboxes with Exchange in your organization and leveraging the high availability fast recovery features of CCR and the automated mailbox management features of MRM, you will enjoy significant improvements in knowledge worker productivity and service availability, at a lower cost per mailbox with improved end-user satisfaction and reduced administrative overhead.
While I mostly agree with the methodology employed in the white paper - disk to disk backups using DPM or something else, the use of CCR, etc,etc no real guidance or methodology is given in terms of best practice. Every IT shop I know runs mailboxes well over the 4GB mark, some in excess of 15GB. Since I'm not the customer paying for the hardware or deciding corporate email policies, it's a moot point to argue that mailboxes should be smaller, since every customer of mine wants to keep all of their mail all of the time. (I'm going to ignore Mail archiving here for a sec)
Where does this leave you - the administrator/owner/IT Pro - etc? If you're running large mailboxes, and large DB's you need to plan for backup and recovery first and foremost. D2D backup becomes a no brainer, and so does some level of replication. DPM is nice here since it Microsoft Backup backing Microsoft Exchange. However, if you're a small shop on a tight budget and worry about restore times, your options are much broader than they were with previous versions of Exchange. No matter your size, planning and testing is going to find the best fit. If you're a small shop, you may want to look at the DPM appliances produced by a number of vendors.
Assuming you're a small shop and you backup up onto tape, then 1/7th incremental backups will buy you a lot, however once your incremental backup times start approaching the length of your backup windows, then the business needs to invest in some kind of disk to disk to tape solution or face a potential disaster.
If you're about to upgrade or move to Exchange 2007 SP1 and have budget for redundancy, then large mailboxes are a real option, as long as you've tried and tested each feature you're about to deploy before you make a promise sign off that SLA to the business. With OST's still in the mix for mobile and/or remote or WAN based users, managing mailbox sizes isn't going to go away in a hurry. Exchange 2007 SP1 with clustering and D2D backup allow for large databases and good recovery times, however, when how does the cost of keeping all the the mail available outweigh the benefit of keeping it available? If you're the IT guy, that thankfully is a question the business needs to answer. If You're the business owner and the IT guy - you have a headache.