For me, I care most about the range of puzzles that the store has and the customer service. To me, customer service includes how fast items get shipped as well as responsiveness, handling of issues, etc.
So, for example, my favorite store is Speed Cube Shop. They aren't the cheapest US-based site (that's Cube Depot, most of the time) but have a great range of items and their customer service is stellar. Heck, they once gave me a gift card because they didn't respond quickly enough to a Facebook message.
My second favorite store is Cube Depot. They don't have a huge range but their customer service and shipping times have always been fantastic and their cheap(er) prices offset the lack of range.
Third is The Cubicle. They have the biggest selection but the worst prices and their customer service has not been good when I've had problems. I'm still willing to buy from them, though, and just placed an order yesterday, in fact.
Then there's Lightake & Cubezz. Lightake has fantastic pricing and selection but their shipping is horrible. They lie about when and where they ship from and take forever to ship (my most recent order took 10 days for them to ship, for example). Cubezz has basically the same pricing and better service but lower selection. However, a couple of the items I got in a recent order were defective and they haven't responded to me so I may have to file a Paypal claim.
Anyway, for me anyway, there's a clear line between the top 2 (SCS & CD) and the rest. And that's because of their service. I'm not a kid, and I have a job, so a couple bucks on a price isn't going to matter to me all that much. For me, it's the other stuff that matters - selection and service.