Trying on is key.
I tried on a Vango backpack in Blacks. It was insanely uncomfortable, but I had no idea just how uncomfortable it was until I went to another store and tried a few Osprey packs which were super comfy. It was only then that I realised just how awful the first one was.
Figure out what you're going to be doing and how much you will need.
A smaller back will allow you to keep it with you more. Some airlines will even allow you to take it on as hand luggage, and when you're on public transport you won't have to let it out of your sight.
The most important thing to do when buying a backpack is to talk to the sales adviser. They are all experts and if you tell them what you're going to be doing they will know exactly what kind of bag you need and can guide you in the right direction.
The second most important thing to do is: don't rush buy. If you need to leave the shop and go for a walk or have a coffee then do it. I guarantee you will see clearer the minute you step outside the shop.
So here is my shiny, lovely new backpack.
*Side note, what is with ALL female travel gear being in varying shades of pink and purple?