Yes - thing to worry about is the load shifting, because nothing was strapped down. Yes, it has happened - Miami, cargo jet, cargo shifted shortly after rotation and the plane went into a 60-70 degree nose up attitude, and stalled. Bad day. CVR indicates that the pilot was stunned and confused.
I'm sure commercial jets have to be able to get in the air with a full load and one or even two engine failures. I'd also guess they run them with small fuel margins to save a few pennies.