Hi Kas,
There is/was an issue with Mapguide 6.5 on windows 2003 SP2. Though I have never tested the x64 edition, i would suggest you run in a test environment for a week or two with some load before you upgrade your existing server to SP2. Its happened to several of my clients and we were not able to resolve it 100% without removing w2k3 SP2.
I came across your post looking to see if Autodesk has fixed this issue prior to upgrading one of my own servers. I just found a post which summarizes a possible solution quite well - but again, i would advise you to test this on a non production server first. It also involves assigning some high powered windows accounts to mapguide which may not be acceptable in some organizations.
http://discussion.autodesk.com/thread.jspa?messageID=5592576