Once upon a time the world was baffled by these peculiar creatures called runners. Some miscreants were even downright hostile. Veteran runners will recall the days before the running boom of the 1970s when running the roads often meant contending with drivers who would hurl not only insults but beer cans, too. These clever drivers would do their best to terrorize the inscrutable runners, even playing chicken to run them off the road.
Well, the bad old days are long gone. Runners are commonplace, and most drivers think nothing of them. Sometimes too little. While runners no longer have to worry about flying beer cans, they do have to worry about negligent drivers. Run defensively and assume that every driver is just plain crazy.
First, a caution against overconfidence. Sure, the law is generally on the side of the pedestrian. Cars are supposed to yield to you at intersections. But that doesn't mean that they will. Assume that all drivers are going to break the law, cut you off, and ignore you entirely. You won't win in a collision with a car. Don't be overconfident, don't cop attitude, and always yield to drivers. If you're running in the road and you have any doubt about an oncoming car, step off the road and out of the way.
In general, though, try to avoid running in the street. Never run on high-speed roads -- it's not fun, and it's very dangerous. If you do run in the road, keep as close to the shoulder as possible and always face traffic. The numbers bear out the fact that pedestrians are twice as likely to be killed when moving with traffic than when facing it. The only exception is at blind curves, when you should run wherever cars from either direction will be able to see you as soon as possible.
In fact, making yourself as visible as possible should be a high priority for any runner who expects to encounter traffic. Bright-colored or reflective clothing is a good idea day or night, and a growing number of companies offer light-weight clip-on lights and flashing gizmos that will draw the attention of the most absent-minded driver (check bike stores if your local running store doesn't have them).
Just stay alert. It's all too easy when you're running to fall into a trance, and if you're running with cars that's no good. Keep sharp, be cautious, and maintain a healthy respect for the nuts behind the wheel. And for that matter, look out for the nuts on other wheels, too: bicyclists and in-line skaters often weave the roads far more unpredictably than any driver, and a collision can lay you up for the duration.