“What is the one best thing that you want a reader to do?” That's one question I ask new clients. Research has shown that offering too many choices creates indecision. To be effective, a call-to-action must motivate your reader to, well, take action. It's not as easy as you might think to decide what that should be. After all, there are LOTS of options.
It comes down to really 4 types of choices. You want your reader to click on something, send you an email, pick up the phone and call you, or come to a physical location. (Let me know if you think of others that don't fit these choices.)
It makes sense to create a list of what action(s) you want your readers to take, ranked from most to least important. Keep it short! Use that list when you design your newsletter. Your list may change from issue to issue or it may stay static for a number of months. Just don't forget that there's a purpose behind your newsletter and what that purpose is.