Most of the fish you'll catch will be on LIVE bait (although you can use artificials to catch certain species).
The first thing you want to do is pick the boat for the task. I usually go with a craft that has greater REVERSE speed (this places less tension on the line and helps you land the fish much quicker). Although you might try a faster turning boat for fish that have blazing turn speeds like Mako sharks and certain billfish, after you're on the water here is where things get tough.
Leave your drag set at the middle.
When a fish strikes, start reversing the boat and try to keep the line and angler (guy in boat) in a straight with each other because it places less stress on the hook and line as well. As the fish starts to become tired there will be more white and less red near the marlin on the fight meter; this is the time to start reeling.
Click on the mouse button as you chase the fish. The added tension will wear them down so they do not run off with your line.
Another thing to remember, especially with marlins and other fish, is that they're very "boat shy." Expect them to start hauling fin when they're near the boat. You also have to watch that the fish doesn't get under the boat; otherwise it'll snap the line automatically.
Try to keep the boat BEHIND the fish, especially when near the boat; then you can park the boat over it as you finish it up.