This should be your first question because the reference might not be using the system. You need to know why. Although a salesperson will usually make sure that the reference is using the system before recommending you contact the company, you should still ask this question. You never know. Make sure that you're comparing apples to apples.
Many large systems have several modules.
It is unlikely that a reference is using all of them. Clients rarely use more than 50 percent of a system's features and functionality. You want to talk to someone who is using the features and modules that you want to use. If the reference is using a system that is several versions old, the new system may have bugs in it. If they've upgraded, ask if the transition was easy.