I have two nVidia cards in SLI powering 3 monitors.

Setup was pretty simple using the binary nVidia drivers on Kubuntu, 0 config file wrangling.

Now, having those three monitors in non-uniform geometries is something I wouldn't even consider tackling

[EDIT]

Kubuntu 12.04

All monitors in a single X Session and automatic application window sizing works as you would expect in KDE

(i.e. Maximising a window maximises to the current monitor only and being able to drag to right side of one monitor causes the window to use up half of the current monitor)