While I very much prefer panniers, my current bike/long bus ride/bike commute has meant that I need to carry stuff on me instead of the bike. If you can swing something like the Arkel, really consider it -- all weather comfort, convenience, etc.

I really really wanted to love my Timbuk 2 medium, but my neck and shoulders rebelled. The one-strap messenger bag thing and my body don't match.

Since I carry laptop, clothes, lunch, and often breakfast (yes my commute is nuts) I needed a roomy, comfy backpack. I have a Jansport Firewire backpack with a suspended (sort of) laptop sleeve that works well and saved my laptop at least once when the bag fell. It's got 2000 cu inches total, including a separate big main compartment and smaller outside pockets for cell phone, sunglasses, etc..it's as ugly/boring as they come though. And a bit heavy. But comfortable shoulder straps and workable sternum strap, and it's held up to quite a beating over the years. If I were to buy again I'd start with the Novara but not sure I could fit everything.

Be sure you either can try it out in a store or get one with a good return policy, because how they carry and how they fit your particular configuration of stuff really matters!