Qsys Interconnect - force usage of "response" signal

That's correct, the response depth dictates how many downstream reads can be in flight. The reason why it's called the response FIFO depth is being read data is technically a response to a read commands.

If you need clock crossing in your system if you rely on Qsys to insert clock crossing adapters in the system then the response information will propagate. I know there are plenty of reasons to use the clock crossing bridge instead of relying on Qsys but I think that's the only valid workaround aside from creating a new clock crossing bridge that supports response signaling.