Graphics - I have an nVidia 6600 dual-head graphics card and it never works out of the box. My xorg.conf will doubtless need some tweaking to get it working.
PHP - as a developer of http://www.carrubbers.org/ I have the requirement of having php compiled with dbase. There isn't a nice .deb package to allow me to do a simple apt-get install.
Zend - I had Zend Studio and Server setup on my old machine and I remember a rather tedious process of getting them to play with each other.
Firefox - from reading other posts, it looks like flash and realaudio won't work in a firefox implementation under AMD64.
I'll post how I get on.