I am familiar with Outlook (in all versions now including 2010). It can be used for large email if you are diligent about keeping multiple PST files and managing their size. The archive feature that creates a new PST with the exact folder structure of the original and moves all messages not touched since a specified date is useful for managing this.
I have clients using Outlook Express with obscene amounts of mail - pushing 8GB - mostly due to emailed pictures and videos. As long as they use folders, this gets factored into a file per OE mailbox. And as long as those are kept below 2GB it seems to be OK.
HOWEVER... The heaviest lifting email client that I have is Eudora 220.127.116.11 paid-version but it is no longer sold. [We originally bought a Eudora 2 user license for version 2.2 and kept updated until the end. I found I can keep a skeleton version of my data tree with almost everything removed and use that to setup a new copy if necessary.]
As of a few days ago this is running on Windows 7 Ultimate in a 2006 era Lenovo 3000 N100 "value notebook" with a Core-Duo (not Core2) @ 1.6GHz, 3GB RAM, and a new 500GB 7200rpm disk.
I have mail going back to 1994 currently at 3,880,090,729 bytes in 18,845 Files, 70 Folders.
Eudora still has by far the most capable filtering I've found. I have almost 2000 rules, most to automatically filter into mailboxes. One killer feature is text search through the filters for either terms in the filter or any target folder name.
Each mailbox is a pair of files .mbx and .toc. Mailbox folders are file system directories.
Attachments are decoded and put into a separate directory. This has advantages (files are already there) and disadvantages (files with the same name get numbers appended and this folder can get very big over time).
The paid version has X1 indexing and search and can do multiple term searches typically in less than a second in spite of the volume of material.
The biggest problem with Eudora (other than it no longer being sold) is terrible handling of HTML email. It manages to display (using IE components) OK but forwarding HTML email mangles it horribly.
I think all email clients currently handle about 10x less capacity than many people expect.
Then there are the EMAIL SERVERS...
Neither the classic mail servers like sendmail and postfix nor Microsoft's Exchange Server ever expected to have users who get and keep Gigabytes of mail.
You certainly don't want to leave much over 1GB on any of these servers. POP3 with "leave mail on server" gets really ugly after a few hundred Megabytes.
The Gmail system of a giant flat store with multiple labels is probably the way of the future but I don't know if any desktop client with that structure. I do know that Gmail offline is not really ready yet, causing various browser breakage in IE, FF, and even Chrome.
The "cloud" will never be acceptable to a lot of people. Therefore for (in)security and privacy concerns I'd prefer a Gmail style server for in-house use along with a somewhat better client than Gmail. Maybe that could begin to keep up with peoples expectations.