You want to shop for a motherboard based on the intended use first. If it's going to be in an HTPC or a system for someone who isn't going to use the features of a full board, you can get away with a MicroATX or so. Full size ATX will have more expansion slots and more features, and often (not always!) have more features than the MicroATX.
Next, you need to look at the CPU. Will you be running Intel or AMD? Since those are the only two choices in the x86 arena these days, its pretty easy to figure out which way you're going to go. Which socket are you going to buy, which processor, etc. You need to match the CPU to the socket on the motherboard, then you can shop for the next bit.
Chipset. Is this an enthusiast PC? Are you going to use the onboard video (in the case with Intel SandyBridge CPUs or the lower end AMD chips that use the onboard video) or are you going to buy a motherboard that has the slots available to expand enough to add the cards you need for say the video card, sound card (if not using the onboard) or any other peripherals (TV Capture, etc)
Next, I would look at the RAM slot capacity and number of slots. Most good full size ATX boards come with 4 slots, and the MicroATX come with 2, but as always, this can vary, so check your specs. If you intend to run a system with a lot of RAM, more slots is generally good, but keep in mind you can get very large RAM amounts with just two slots. The downside of course is that if you upgrade to more memory later, you have to toss out what you already have.
Lastly, I would consider specs of the motherboard. Does it support SATA 3? USB 3? Are you using those kinds of components? Do you even care? If you're building a money saver low power system, probably not. But for a cutting edge gamer or power user system, it might be worth it to spend a few extra bucks.
That's just the basics. I'm sure others will chime in with their recommendations.
