Are you getting a lot of responses back from contacts who are out of office when you send out your email campaigns? I do agree It would be nice if Marketo had some support for reply management but that’s not in their roadmap I was told.
One thing you could do is look into dedicated hardware to filter these types of messages so they dont hit your mail server. Cisco's Ironports are great options that have a host of filtering and security options. It acts as a relay server so incoming mail goes through there first and then based on rules and logic gets passed down to your internal mail server. They are made to handles extreme volumes of mail. Im sure there are Saas options as well if you dont need or want to invest in additional infrastructure.
Chris makes a great point. Adding an additional layer to your email system will allow your servers to handle this additional load.
One other possible option (which has other downsides) is to use an alternate domain for sending your Marketo emails, and set up mail on that domain on another system that isn't on your corporate network. In other words, set up hosted email at a commercial hosting service just for email for alternatedomain.com, and then send your Marketo messages from firstname.lastname@example.org. This would allow the other system to handle any replies.
The downside to doing this is the credibility hit you take from using an alternate domain for your marketing. If you're going to go this route, make sure the alternate domain is clearly tied to your brand, and that your branding on your messages is really tight. You might even want to send an introductory email from the old domain one last time to let people know that they can expect to receive your messages from the new domain going forward.