I was thinking about this the other day actually as someone else was talking about having thousands of them of their site and they were worried it was going to hurt them.
Question for the techies - is is possible to automatically redirect all 404 pages to a subdomain that's noidexed? Eg: 404.yoursite.com rather than yoursite.com/404.
Idea is to just get them off your main
www.domain and deal with them elsewhere to try and reduce the risk of any negative implications. No idea if it'd work, just thinking out loud really...