Technology too ahead of its time and difficulty getting the market to come along with the company story. It can and does work, but when dealing with crufty old, technology-phobic clients, can be a real challenge.
Too narrow a product focus and operations side has problems delivering in a speedy fashion - somewhat driven by a disconnect between sales and Ops.
VPs/C-level management hiring too many "big company" people that can't adapt to operating in a very small company environment. Far, far too much focus on process and not enough on getting stuff done.