The biggest problem is failing to make a product that some users love, but then thinking they will solve their problems by doing everything else well.

The second-biggest problem is probably cofounder fallouts.

Internal communication and management structure are always big problems for growing companies that I wish someone would solve.

Hey Sam, re: solving internal communication, you should checkout a non-profit called http://www.helloinnerspace.org/ funded by this group called YC ;)

Seriously though - after attending their cofounder communication workshop, we invited them to do it for our whole team. I think Innerspace is the best tool I have seen to prevent cofounder fallouts and improve internal communication.