I picked one of these up a couple months back, and it's been great so far. I don't have a ton of gear, but that means that I have quite a bit of flexibility in deciding what goes where. I have three main configurations:
Light. This is mostly for around town.
Canon 450D w/ Sigma 50mm 1.4
Canon PowerShot S90
18-55mm kit lens in case I want a wider angle
iPad in the laptop pouch
Cables, adapters, etc in the various pockets
Heavy, for when I leave town. All of the above, plus:
15" MacBook Pro, charger, camera battery chargers, and the MiFi charger.
500gb portable disk
Diaper. I'm a dad, and this backpack is big enough to hold the light configuration, plus a second iPad, diapers, wipes, a change of clothes, bag of snacks, and a couple books and toys. I sometimes leave the kit lens at home, since the S90 covers most of the same range and it's easier to pull out than swap lenses anyway. I can actually (barely) stuff the laptop, charger, and disk into there, too, but I don't usually need to.
Even loaded to the gills, it's not terribly uncomfortable. My only complaint is that the tripod straps on the side are kind of lame. They'll hold my tripod fine, but it becomes impossible to set the bag down and the balance is totally whacked. Some have a center read-mounted tripod setup, and that would be much preferable — but at the expense of easy access to the contents. The one other thing is that it's hard to use the last couple inches in the bottom because of how the flap opens. I don't mind, I just put the larger / less frequently used stuff down there.
Otherwise, it's been great. I love that it sits upright when I put it down instead of falling over, and I feel much better about having the camera up at the top of the pack instead of on the bottom.