First of all, it depends if you have to commute to an office in some industrial park (even if it's only one or two days a week).
Then there's the question of where your friends live, whether you regularly do activities outside the city, etc. Zipcar and Uber definitely make it easier not to own a car. But my observation of people I know in SF who don't own a car is that they make ample use of both Uber and regular/short-term rentals. People can definitely get by but it's often by adjusting their lifestyles and activities in that you just don't do things that are hard to do.
If your goal is to avoid any sort of exercise (and the "forced" exercise is one of the biggest reasons to go carless in my opinion) then yes large sections of US cities may seem inacccessible without a car. But if you like walking like I do (at least up to a half-mile or so) then you can live just fine in US cities without a car, in my experience. I've done it all over.
Even given a decent commuter rail system it doesn't help for those sorts of activities.
So it's not really getting around the city but getting anywhere outside the city that isn't on convenient mass transit.