I just returned from a 12 day trip to Peru that included international and domestic flights and train travel. I onebagged it with an Eagle Creak Gear Hauler and had a Pacsafe Metrosafe 250 GII as my day bag. It has a lot of nice security features as Shak51 pointed out.

During flight I would stow the Gear Hauler in the overhead and the Pacsafe under the seat. I kept all the items I needed access to during flight in the Pacsafe: iPad, headphones, snacks, wipes, camera, pens for immigration forms and documents. When sightseeing I would use it to hold the camera, drink bottle, wipes, maps and small travel gnome/mascot.

Prior to departing I was hoping that I wouldn't have to bring my 15" laptop but my freelance clients said there might be work to do. So it came down to the Pacsafe Venturesafe 45L and Eagle Creek Gear Hauler. Both hold similar loads in their main compartments, but I felt the EC was able to accommodate my laptop better. Interestingly I felt the EC was more anti-pickpocket because the backpack straps are on the front side of the bag where all the compartment zippers are, so the zippers are against your back when you are carrying it. There is a handy 'trunk' compartment at the bottom that is exposed, but I just used that to carry an umbrella, cheap sandals, strap and a Pacsafe 85L safety web bag.

My main objective with the Gear Hauler was to be able to carry on my clothes and laptop on all the flights and it worked well. Even when fully packed it looks small as a backpack and I managed to get it by the check-in (weight with the laptop was around 22-25lbs). As a side effect of this last trip I have been inspired to keep onebagging it (or should it be 1.25 bags with the Metrosafe?). The EC may not be as burly as the high end carry-on bags like Red Oxx, Tom Bihn or MEI, but for the price I paid for it I am definitely happy with how it performed and will probably use it till it wears out. At that point I may look into the high end bags.