Windows 2008 R2 is 64 bit only. Quickbooks Database Manager (hereto referred to as QDM) is only certified on 32 bit systems from what I've read. Setting aside how ridiculous it is in 2010 that Quickbooks doesn't officially support 64 bit systems, I had to make a small adjustment when configuring QDM on Windows 2008 R2.
When I ran the Quickbooks connection diagnostic tool, it said I had to open ports 8019 and 55338. Weirdly, I never had to do this for previous OSes, but c'est la vie.