Eudora, no contest.
I've got >42,000 emails, from just now back to 1991, in a dozen mailboxes and I can search them very quickly based on email body, To, From, CC, Subject, or any other header, or attachment name, or date range, or label, or any of several other search parameters or any combination of them, and the results can exist as a permanent window like as OS X "smart folder".
I get spam-bombed all the time (I'm stubborn and don't want to keep changing my email address, so mine have been "out there" for a long long time) but I have a FORMIDABLE array of filters (about 4600 lines' worth) and somewhere between 99.75 and 99.8 % of my spam is caught, labeled, and trashed, and the rest of my email is nicely sorted, assigned to an appropriate account ("personality"), and may beep normally, give a special alert beep, or not beep at all depending on various parameters.
EDIT: Oh, and also, you never see people come in here and post "Eek, my Eudora mailbox got corrupted, Eudora won't open it, I've got a bunch of important emails in there I need access to, whatever shall I do?". The Eudora email file format is plain text and can be scavenged and/or edited with BBEdit or TextWrangler very nicely. I once had a massive hard drive directory-structure snafu (HFS Catalog file hosed under MacOS 9.0.4) and the folder containing my Eudora folder and its mailboxes just turned up missing. Did a text-string scavenge-and-recover and got zillions and zillions of text fragments and was able to pipe them into Filemaker Pro, sort them, and export them with delimiters as a Eudora mailbox file and then mass-move them to their proper Eudora mailboxes easily enough.
EDIT FOR TYPO: 99.8% originally entered as 88.8%