Can't address more than 4GB in 32bit mode...if that matters to you.
The primary hangup for this is your video card. Windows maps video memory into physical address space, so if you have a 768MiB video card and 4GiB of RAM, you can only see 3.25GiB of memory in Windows in x86 (32-bit), although you MIGHT be able to work around this with PAE enabled. I run x64 Windows at home; aside from some initially shaky driver support (I got it at RTM, two months before retail launch), I've had zero problems with it, and I get about 0.2 extra tick points out of my CPU on the performance measurement tool.
To re: to warz' comment: there are extra folders:
c:\Program Files (x86)\ -- this is a place where 32-bit programs are installed. Native x64 apps go into c:\Program Files\ still.
c:\Windows\SysWOW64\ -- this is the place where all your 32-bit c:\windows\System32 files would go (since 32-bit apps need to still dynamically link against the 32-bit libraries).
Off the cuff, those are the only "extra" files I can think of (I'm on my work PC right now).