Yes, it's a lot of work to get a reference customer on board and a case study signed off, but there is a time you'll have to let go. Great customers become good customers, become bad customers.
The process is gradual, so when is the right time to break the tie? While you'll probably be in touch with most of your references on a regular basis, make sure that you keep tabs on all of them and give each reference a call at least once a quarter to make sure that they aren't having problems with your product and that they're still using it. Don't let your prospects be the ones to find out that your public reference moved on to a competitor.
Make sure that you update each case study at least every year (some people recommend 6 months) so that you're not advertising outdated technology. Otherwise your prospects may think you're not cutting-edge.