During the mission-planning phase, make sure to plot the waypoints for
your ingress and egress routes around enemy antiaircraft concentrations.
Although it may take longer for the bomber fleet to reach its objective(s),
the formation won't have to fly through as much flak, which will hopefully
cut losses and make your bombing run that much more effective. 

Don't forget that in addition to the bombers, you can take over the controls
of your fighter escorts at any time during play. Consider hopping in the 
fighter escorts during the early phases of the mission to keep the enemy 
fighter opposition at bay as long as possible. You can always switch back
to the bombers whenever the enemy fighters are within attack range of the
bomb group. 

If you're playing the bomber campaign, don't bother going after distant 
targets such as Berlin until the spring of 1944, when long-range P51D 
Mustangs are available to escort the bomb group to and from the target.