It is simply app specific. There is a highly robust x86 emulation layer in x64, but there are some proggies that may still be broke, or were only fixed in the latest version.
There are compatibility lists out there, but if you want to to do it mega-comprehensively, check out the
Microsoft Application Compatibility Toolkit 5.0 (
http://technet.microsoft.com/en-us/windows/aa905102.aspx)
Other considerations are:
*drivers for your hardware and peripheral devices.... CHECK, or risk disappointment!
*codecs. This has been pretty much sorted with the VCP/x64 components, but some tweaks/factors be aware of.
Let us know what app/games you play and I can fill you in. A couple of us here run vista x64(including myself) so should be able to answer directly.
With that, I would like to say that unless you are doing some higher end video/design/graphical/processing stuff, the advantages for an x64 switch are minimal. Most apps and games arent x64 optimised > simple as that.
I simply have x64 on because I do alot of HD video editing and x64 with 4+GBDDR2 makes the pure crunch in rendering/encoding in these specific apps happen quicker.
mtfbwya