Running on different surfaces, or cycling, or even working out on the elliptical machine at your gym will activate a variety of new and different muscles. If your body is use to running on the treadmill, increase the incline or take a run through your local park. If you are a trail runner, try mountain biking. When you start to vary your terrain, add inclines and descents, cross-train, or even run in different shoes you increase your strength and activate muscles you may not be currently using.
For example, swimming is a great full body workout with impact. Upper body and core strength are important for a runner and swimming is a good way to help you achieve an all over strength gain. You can, and should, also incorporate strength or resistance training into your daily routine. This will make you stronger, fatigue less quickly and become more toned. After a strength training session, your body burns a lot of calories and needs additional energy to repair the muscle tissue just broken down, therefore increasing your metabolism.