Yes, I did try it without, and in fact the from and reply to work just fine.(with or without) It's more an issue of the "Return-Path". I'm not totally familiar with how the junk mail filters work, but I suspect that some systems compare the domain in the Return-Path with the domain in the From or Reply-To fields in making a determination as to whether or not something is "junk". Thus, from my hosted server, lets say "jupiter.net", mail from my domain my ends up configured as:

Return-Path: baseuser@jupiter.net
Reply-To: me@mydomain.com
From: me@mydomain.com
To: you@yourdomain.com
[download]

That said, for some reason this doesn't appear to be the case with all receiving domains. For example, when I send mail from me@mydomain.com to me@seconddomain.com hosted by a different company on a different server, the Return-Path appears as I instruct MIME::Lite to display it. (and vice-versa). However, when I send it to me@pacbell.net or me@aol.com, I can veiw the code and see the the Return-Path is "reverted" back to "baseuser@jupiter.net".
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Filmo the Klown