The wasting of draft picks can be directly attributed to the constant coaching changes. With a change of coaches/GM, there is a change in philosophy and with that comes wasted draft picks if the previously drafted players do not fit into the new scheme.
And as Bill in NYC would love to say, "We spent too many 1s round picks on DBs" and then we don't re-sign them after their first contract.
The other issue is the Bills staying in the Mediocrity part of the standings...They are never at the rock-bottom or at the top...So they miss out the opportunity to get a blue chip prospect.
And finally, when they had chance to take QBs, they took the wrong one. If it is a QB driven league, you got to get the QB right!!!