But cashiers/servers probably get asked that same question "how are you?" a hundred times per day. Customers who think they are being nice by starting small talk may have the opposite affect. It's all context really.Small talk in a busy line is probably not the best idea.

It all depends on the person, and there's no way to tell without asking. If someone doesn't want to talk, it's quite easy to tell from their response to the question. If that's the case, you end the conversation there, and nobody cares.

Anecdotally, I have started many conversations with service people this way, and I'm not much of a talker. In fact, it's usually them telling me about how horribly things are going, and I just listen. It's interesting how often a perfect stranger will open up to you if you just show a little empathy.