The less traffic on the road, the fewer hazards you will meet. Try to avoid city driving when people are rushing to and from work in the early morning and late afternoon.
Although through streets make driving easier and more direct, everyone else uses them for that very reason, too, so expect some traffic. It is generally safer and less stressful to take side streets, though, even if it may take you slightly longer to arrive at your destination.
One-way streets are safer than two-way streets, where oncoming traffic may drift or swerve into your lane.