I'm using Win XP x64 Pro/4Gb RAM and don't have a problem with it except:-
1. My accounts program doesn't work (expecting an update for XP x64 and Vista x64 later this summer).
2. Check online forums for the motherboard you are intending to buy as some have problems if all 4 RAM slots are occupied.
Check all your peripherals (printers, internal modems, scanners etc.) have 64-bit drivers. I had an Epson laser printer and although it had a 64-bit driver for WinXP x64, it was very rudimentary compared to the 32-bit driver. When it died on me I did a thorough web search and replaced it with a Lexmark C534dn which has wonderful drivers and is a much better printer. Epson still haven't released 64-bit drivers for my scanner - but not too worried about that as I only use it around 2 or 3 times a year now, and when I need it I just hook it up to an old XP x32 system and bring the files in across the network.
Gretag-Macbeth has drivers for their Eye One Display 2 pucks and these work well on Win XP x64 - but they still do not have drivers/software for Vista x64, even though they have been promising these since late January.
2Gb memory sticks are now at around the same price as 2x1Gb sticks - so I would recommend that you go for the former as this leaves space for an additional 4Gb should you decide to up the RAM later. I am contemplating going to 8Gb in early June - but this means I will have to sell on my 4x1Gb sticks.