I've just test an ATI FirePro 2460 graphics card on CentOS 6.4. It connects 4 monitors. It worked with the standard radeon driver. I was able to arrange the monitors into my preferred configuration (as a square array, 1 upper left, 2 lower left, 3 lower right, 4 upper right) simply by clicking System -> Preferences -> Display, and then moving the four monitor images. This creates the file ~/.config/monitors.xml .
Moving windows among the monitors worked smoothly. I did not install the proprietary ATI driver; I don't need any of its features beyond what the standard driver provides.
Some details: Dell Optiplex 9010, Small Form Factor (SFF) case requires SFF cards. CentOS 6.4 fully updated as of today. 2.6.32-358.2.1.el6.x86_64 kernel xorg-x11-drv-ati 6.99.99 1.el6 x86_64 BIOS shows the board in slot 1 (the blue connector) as "VGA Compatible" lspci shows 01:00.0 VGA compatible controller: Advanced Micro Devices [AMD] nee ATI Cedar [FirePro 2460] Kernel driver in use: radeon No xorg.conf was created or required. 4 Dell 2007FP monitors, each at 1600x1200 connected via DVI.
I used to use Matrox M9140 cards, but that requires the Matrox proprietary driver which has not been updated for CentOS 6.4 as of today.
I also tested two other cards: ATI FirePro 2450 and NVidia Quadro NVS 420. For each of these cards, the BIOS shows the card in slot 1 as a PCI Bridge. lspci reports two identical video cards at 03:00.0 and 04:00.0. Though it's easy to set up two screens properly, xinerama would probably be required in an xorg.conf to get all four screens working properly.