Weight, weight and weight.
You can beef the vehicle up but you quickly wind up with no usable payload. Long past time we developed a new vehicle. We have much better and lighter weight materials and systems now.
Which gets back to the design of the shuttle. It's not really the most economical or the most efficient way to boost large payloads into orbit. Yet, it is marketed as such. Since it is marketed as such, safety has been compromised IMHO.