I've only used a suitcase on one vacation, when I flew to Las Vegas for a wedding, and was planning a couple extra days driving around the South West US. First, because I was bringing a suit and needed a clothes bag, and second, because I knew I'd be renting a car and wouldn't need to walk long distances to hotels via public transportation. For every other trip I've used a backpack or duffel bag.
I find it so much more convenient to have a backpack. It's easier to go up and down stairs with, and when you need to cover long distances.
When purchasing a backpack, here are some tips:
1) Make sure it is waterproof!
Since most backpacks are intended for hiking/camping they should be, but check. When I was in Australia the hotel staff carrying our luggage from the boat to our island dropped ALL THE LUGGAGE into the ocean. My pack was completely submerged, yet when I opened it up my contents were bone dry. Unfortunately my friends were not so lucky.
2) Before you buy it, make sure you can collapse the pack in such a way that there are no loose strings, lines, or belts.
Most important is to make sure that the hip belt can be reversed around the backpack and fastened to form to the backpack. I purchased a Gregory backpack and it had plastic hip moulds that would not allow you to do this. It can get snagged on an airport conveyor belt. Avoid it.
3) It should have multiple access points.
Having access only from the top means you have to take everything out to get to the bottom, which not only gets old real fast, but becomes a nightmare if you packed it tightly, and now when you toss everything back in nothing fits. A good backpack should have access from the top, front, and maybe bottom.
4) Personal preference, but I like backpacks that have a sleeping back compartment. First, in case you actually end up needing to put a sleeping bag there, but second it's a great spot to place dirty clothes, or your day bag. Then, on the way home it's empty and you have room for souvenirs.
5) Size.
I have a MASSIVE backpack -- one of the biggest, a KELTY Red Cloud 6650 at 109L. I feel like an amateur walking around with the huge thing when everybody has much smaller ones. Don't go that big. I have yet to find the best size.