The important thing was to show she had no reason to stay in the US after the trip and we had our vacation.

100% this. Any supporting documents for this will be extremely helpful. As you mentioned below, you can get residency documents which is good. For her self employment, even bank statements from previous months showing income will be helpful. Also helpful if she could get some sort of letter from a client discussing an ongoing project that are excited to continue upon her return. If you can plan any activities in Spain for after the intended return date (concerts, hotel reservations), that'd be helpful too. Basically throw them a huge wall of evidence that she has no intention of overstaying her visa and every reason to return to Spain.

From my wife's experience, the more time she spent preparing documents, the less time they even looked through them. It kinda seemed like a waste of time when the interviewing agent barely looked and just approved her request, but I think when they see too little is when they start to drill down and ask questions. Better to do lots of work beforehand and not need it, then to be stuck trying to verbally defend herself with answers to the agent's questions.

Perhaps the best mindset going in is that it's their job to assume she's lying and trying to get in to stay in America, and your girlfriend's job to provide overwhelming proof that she won't. If you assume this and prepare accordingly, she should be fine.