Zippers are always a potential point of failure, as are clasps, buttons, buckles and, to a lesser degree, snaps. You'll often see a metal zipper head paired with plastic teeth, as all-metal zippers may rust or stick. While it may seem tempting to get a bag with a bunch of bells and whistles, it's best to keep it as simple as possible. To keep zippers as waterproof as possible, main compartments should be covered by a flap of edging fabric (again, check out that classic Jansport design) or be waterproofed by shielding the zipper teeth from exposure, as seen on the Booq Cobra Squeeze.
External storage should largely be zippered or sealed so that your items can't fall out. Keep in mind, too, how easy it might be for thieves to access these sections. Internal storage will often consist of open "'slip"' pouches, along with a zippered pocket for cables. As you look at potential bags, think about what you would want to keep in each pocket, and how frequently you'd need to access it. Also remember that you don't have to rely on your bag's storage sections alone. I use a Mission Workshop Arkiv tool roll to corral my cables, chargers and batteries. It rolls up neatly, leaving the external pockets on my bag available for things I need to grab quickly, like transit cards and headphones.
Padding and support
Padding in the back panel is essential when it comes to comfort -- mesh will breathe better, but it won't bounce back as fast as foam padding. Channels built into the back padding should provide some relief to those who tend to sweat a lot. There should also be some padding in the shoulder straps. If you have back issues or commute on two wheels, make sure you get a sternum or waist strap on your bag to help secure it to your body and redistribute the weight.
Stitching and reinforcement
Pay attention as well to how the straps are attached to the bag, at both the top and the bottom. The bottom straps should be sewn into a bit of triangular reinforcement fabric that attaches to the body of the bag, not sewn directly into the body of the bag itself. The stitching on this triangular attachment will often be reinforced, resembling an X or an X in a box.
The tops of the straps should also be in some way reinforced to the back panel, as seen in the Fjällräven Kanken, which has a distinctive X shape, or Mission Workshop's Sanction, which has two attachment points to adjust the fit. Speaking of adjustments, watch out for buckles or hardware on the straps -- they may sit or rub uncomfortably when worn.
So what should I get?
If you need a professional yet feminine style and aren't worried about weather or pickpockets, then check out some of the offerings from Knomo or Tumi. If you need something professional, or at least business casual, in more of the briefcase style, consider the options from Defy, Timbuk2, Waterfield Designs and Filson.
If you want a traditional messenger, then you're squarely in Chrome, Mission Workshop and Timbuk2 territory -- but there's a lot out there, messenger-wise, so keep in mind other great manufacturers like Rickshaw Bagworks, Vaya and Freitag. If you need a zippered backpack, there are great options from InCase, booq and Briggs & Riley; also Knomo, Aer and Tom Bihn. If your style is more rolltop backpack, then you'll want to see selections from Chrome, Timbuk2 and Filson as well as those from DSPTCH, Inside Line Equipment (ILE), Thule and Fjällräven.
Whatever style you wind up selecting, keep a close eye on the construction and materials -- stitching should be snug and uniform, hardware should be sturdy and functional, compartments accessible and thoughtful -- and keep in mind how you want your bag to fit to your body. As with any tech purchase, you want to get what you pay for: a quality product that suits your needs and lasts for years.