Not that large mailboxes, but a couple ones in and around 300 to 500 MB. Windows 7 Pro, 32-bit. Accessing mail server via IMAP (six mailboxes, 'bout 2 GB all in all), two via POP3. No slowdowns; no CPU hogging, no excessive memory usage (hell, Live Messenger is using up 58 MB right now, Thunderbird only 44 MB). CPU usage at 0 at almost all times (seen it jump to 8% on my dual core 2.33 GHz Intel machine). I/O performance is great, too.
I don't know... Seems to me that people are just trying to create solutions to non-existant problems, and most likely in the hope of being able to sell it to someone.
If they do find a solution to the excessive memory usage of Firefox, or it hanging whilst running the Java download manager from Microsoft, I'll cut' em some slack.