What ever flow control method (or lack of) you use for serial transfer you will want the physical and logical formats to be appropriate for the ammount and frequency of data transfer.

Streaming un-packetized data is often the case where physical flow control enters the fray.

Packetized data is well handled by the old 3 wire exchange.

The serial data exchange challenge is found in the buffer department.

You have not mentioned alarms (DSR,CD) they are another case where additional signal points are useful.

regards,
p