1- Use nine words or less. That's all the room you've got. If not, people's eyes will glaze over and they'll ignore your board.
2- Use distinguishing colors. My boards colors you would associate with a landscaping company. I use bright yellow letters on a bright green background. No one else is using those colors, so it makes us stand out.
3- For God's sake, if you are doing multiple billboards, use the same design. There is a concept in advertising called frequency (or impressions). You are getting more impressions when people go past the same billboard in various places. Given that a customer needs to see an ad eight times before they make a decision to call you, by being consistent, you are increasing sales geometrically. And the same goes across various mediums, my yellow page ads all use the same format as my billboard. One day, when I start doing TV ads, they will be consistent with my billboards. The more consistent you are, the better. Your average person sees millions of ads a year, and by being consistent, you are making yourself more prominent in their mindspace. Let's be clear - you are fighting for mindspace, and nothing else.
4- Put up billboards where your target customers are, and not where they are cheapest. None of my competitors have followed me to where the big corporations are. Two of them have put up boards in the lowest HHI areas, because they are cheaper. Both of them are not doing well. If you want to gain millionaire customers (or upper class or upper-middle, or middle class customers) put up boards where the live, work and eat and shop. If you think you are going to sell luxury products in the part of town where blowjobs go for .50 cents, you are mistaken. Yet, a lot of business owners make this mistake. One of my competitors put a billboard across the street from my place of business. Sounds smart, except we are in the part of town with very few residential customers, and customers don't visit our office. Duh.
5- Listen to your creative counsel. The reason why a lot of billboards don't grab anyone's attention is that the owner overrides counsel. They pick colors that don't stand out (I once saw a business do dark maroon letters on a black board, you couldn't even read the print, what a waste of 1k a month) or they put 50 words on the board (and no one wants to read it). Most creative counsel isn't going to fight the decision maker too much, for fear of losing the contract.