I just built my m-itx Bitfenix Prodigy gaming computer and I love it, but there are definitely things to know about building in some of the smaller form factors.
For m-itx, most cases restrict you from using full size gpus and large heatsinks. The Prodigy and a few others change the orientation a bit to get around this. However, as far as I know there are no m-itx boards that support multiple gpus in crossfire/sli (I don't see how they could possibly fit that in), many m-itx motherboards limit your choice of cpu heatsink because it either interferes with the pci-e slot or the backplate touches things it shouldn't (only really matters if you plan on overclocking). You also have to pay extra attention when choosing a power supply, some just won't fit and others might technically say they will, but are a real pain to smash in. Also, most m-itx boards only have 2 ram slots, limiting you to 16GB of ram, which is more than most people need anyways.
For matx, you get a lot more flexibility, and can usually have everything you would find on most full size atx boards. You can use 2 gpus (I don't think there are any that allow more than 2), and the cases usually fit most standard sized components. You do still have to pay attention when choosing the case, as some don't fit larger GPUs or tall heatsinks.
For ATX, you of course have all the options available, I'll just list the things you CAN POSSIBLY have access to if you get an enthusiast motherboard (or perhaps an extended atx). You can possibly have up to 4 GPUs, up to 64GB of memory, a dozen or so disk drives, and generally more space means better airflow for good cooling.
I decided I wanted a smaller system, and had been planning a matx build. I changed my mind and went with the Prodigy and an m-itx build because I liked the look of the case and wanted to try it out. I decided I didn't need SLI, and I only planned on using 8GB of ram. I don't want an optical drive, though I could put one in, and I don't need a bunch of internal drives. I am using one large SSD and the rest of my storage is external, although I could still put in like 9 drives if I so desired. My airflow and cooling is excellent, and because I wanted to overclock I tossed in a huge Noctua NH-D14 cooler. I run at 5.0ghz, I just loaded up Far Cry 3 and The Witcher 2 and both run beautifully at max settings at 1920x1080, the system is extremely quiet (near silent compared to my old Phenom 955 / 295 GTX system), and I like the smaller size and overall look of the system.
If you don't need extra GPUs or a million disk drives, I say go for one of the smaller form factors. I chose an ASUS m-itx motherboard, though I would have gone with the ASRock if it was compatible with the NH-D14. If I had gone matx, I had my heart set on the Asus Maximus V Gene board, it is more expensive but I loved the features. Good luck with whatever you choose!