I have been running 64-bit Vista for years. It's mostly a pleasure, but I can pinpoint two problems I have had with it:
Java JDK 64 bits can be tricky. Some frameworks won't integrate well with it, and it's not as up-to-date as the 32 bits version. Though I'd love if someone came and told me that is no longer the case -- I have learned not to try it a long time ago. :-(
64 bits software is not as prevalent as might be desired yet. This is mostly a non-issue, as you can run 32 bits software just fine. But when it comes to software that integrates into the explorer menu, it matters.
As an example of the later point, I have TortoiseSVN running fine on my explorer, but TortoiseHG wouldn't show it's menu there. There was a work-around, which was running explorer with an option which will force 32 bits (%windir%\syswow64\explorer.exe /separate). I needed a shortcut for that, though, and the 64 bits stuff (TortoiseSVN! :) won't appear there.
Edit:
BUT, as of two weeks ago, according to Mr Spolsky, it is now working. I should have it running as fast as I can reboot (Windows, duh!) this computer. Which is all the more proof you should go 64 bits. :-)