Like most one-strap bags, it's at its best when moderately loaded - the strap is wide and well padded, but it does get awkward when loaded with heavy items - I wouldn't use it to carry a couple six-packs of Coke cans, for example.
With moderate loads, it's very comfy and stays in place nicely. Backpacks are vastly better for carrying real loads any substantial amount of time. One-strap is fine for light loads as long as need be, and heavier loads for proportionately shorter periods. I find that anything over about 7 or 8 pounds of stuff makes me wish for a backpack in less than half an hour of lugging. Your mileage may vary.
On-off is actually easier than with backpacks - just reach up, pop the strap over your head, and it's off. Alternatively, release the buckle, and it just falls off. The only time the over-your-head maneuver is odd is if you've got head gear - a baseball cap is a little in the way, and a bike helmet can make it near-impossible - but that's what the quick-release buckle is for.
You can get into the main pocket and the front flap while you're wearing it, but it's a touch awkward - better for reaching in and pulling out a rainshell than for finding a pack of tic-tacs, in that you can get a hand in, but it's a bit hard to get a good view inside the bag, at least for me.
Worth noting that the one thing I still really don't like about my Typhoon is that it's a left-handed bag, with the single strap set up to run from right shoulder to left waist - it's made this way to avoid getting in the way of all the stuff that people clip on the right side of their belt, from cell phones to flashlight sheaths to concealed weapons, but since I don't carry anything there on a day-to-day basis, I'd really prefer that it oriented the other direction.