In my experience they both require setup. It is hard to say which one will be "easiest" because that is largely dependent on the type of work flow you would be most comfortable with. Ultimately this is a question best posed to the developers. Give the setup tutorials a read and see which one seems to make the best sense to you.
It isn't really like "x" is super easy compared to "y" It is more like "x" is easier in these ways but more complex in these other ways so they are both going to require a learning curve but because we all think/work differently you will find one to be a better option.
That said, I like WooCommerce for myself right now. That might change in the next generation of the various carts, I know WP eCommerce has an update I haven't tried and I think cart 66 does too, so my experience might be a bit dated.