Not enough memory + ISS Problems?

It sounds like you are in a bit of a corner in regards to the amount of memory you have available on chip.

If you are using onchip memory for your code, then a recompile in quartus will quickly swap in your new code into your sof (without a full recompile) and you can redownload your sof to update your code. You are then limited to printf for debug.

It is possible to build/download/run without an OCI core and without updating your sof, but unless you are running from flash and can burn some code into it, the solution will take more onchip memory than the OCI core does. Also once you make this choice you are operating in a much more primitive mode and you will have fewer tools and have to manage more issues yourself.

To download code without the OCI core you must use the "Legacy sdk" (check the Legacy sdk support box on the More cpu_x settings tab).

If you are running from external flash then you will want to burn the monitor into flash and run it after crt0. You will also not be able to debug with the IDE. Unless you port the gdb stub to Nios II you're debug method with actual hardware will be limited to printf.

Once germs is executing on the CPU you can use the nios-run command to talk to it and download new code.