I go for the big rolling duffel when I need to transport a lot of equipment. Usually, this means trips to places where I need large bulky clothing and clunky boots, in addition to other equipment. For me, these have been trips to Antarctica, Arctic Norway, rafting trips in ANWR. I use a 30" Eagle Creek ORV Rolling Duffel. The weight to space ratio is excellent, and I like the little features like locking zippers, outside pockets, and separate internal compartments. What's nice about the duffel is that I can collapse it far more than an upright, it's generally lighter, and it accommodates strangely shaped items. I usually have enough clothing or other soft-sided gear to provide protection for fragile items. I've also got the Eagle Creek packing cubes and other things to organize things.
When I was younger, I would just use a large or extra-large size North Face expedition duffel. Bear in mind that when I was younger, I had no problem lifting a 50 pound duffel on to my shoulder and running through an airport with it.
One of the considerations is what you intend to do with your luggage at your destination. Wheel-less duffel bags are very easy to compress and store, whereas an upgright or rolling duffel is less so. If your travel is in urban destinations or via car, then it doesn't really matter what you take - as long as it fits whatever size and weight restrictions you need to deal with. If you're wandering cobblestone streets or hopping buses or pangas in third-world countries, then a backpack is really the way to go.
For simply urban destinations, I tend to go with a good size daypack, my rolling 22" carry-on, and a collapsible duffel bag. My carry-on carries a week's worth of clothing and whatnot, which is all I need. My daypack carries camera equipment (which is considerable) and laptop, as well as other electronics. The collapsible duffel is there to carry back any souvenirs I may have picked up along the way.