I have not really tried to use 64bit Linux with the exception of an short and aborted experiment with Ubuntu 6.06 64bit. Now that 64bit OS becomes more popular and I think I will give it a try. Ubuntu 9.10 64bit is the nature choice since I am at home with Ubuntu after using it since 5.04.
The fresh installation (using ext4) was a very smooth process. The installation cd is also a live cd. So I could try it out before real installation. The live cd could not run at full resolution with my Nvidia card but this was expected. With the proprietary driver from Nvidia, the display worked fine.
For the fresh boot, X did not work, complaining the module nvidia did not exist. That was not a problem. I boot with the vesa server and then install the proprietary driver and reboot, X worked fine again.
Flash player is no longer a problem with this latest Ubuntu 64bit OS. So that is a good sign.
Media (mp3, xvid coded avi, rmvb, etc) playing with Totem and VLC is in general fine as well even though some old RMVB file are still a bit problematic.
Firefox occasionally still crashed and that is again expected by me. It is the single most often used and most often crashed program for me under Linux.
I have some programs (gputils, sdcc, openocd, pk2cmd and some other libusb related programs like pyusb and lpcusb) and recompiling them is in general quite simple. I could not find old glib-1.2 related packages in the repository but I will try later (Edit: download glib-1.2 and gtk-1.2 related packages from Ubuntu 9.04 x86_64 and they seem to work fine for Ubuntu 9.10 x86_64).
So in general, Ubuntu 9.10 64bit seems to work fine for me now.