I always go with two smaller bags. There are a lot of benefits. I use an expandable Swiss Army ruck sack ( stuffed), and a soft side satchel, (yuppie briefcase) Swing the smaller in front of you will distribute the load, and take the pressure off of your lower back. This also makes it a lot easier to get through crowds, on buss's etc. When you hit a destination, you can use the satchel as a day bag, and not look like a tourist.
If you're flying, the satchel becomes a carry on, loaded with the basic essentials, in case your other bag is lost or delayed. all of the non carry on items, pocket knives, can openers, non factory sealed containers etc. go in the larger checked pack.
I've tried a lot of other ways, this is the best system by far.