Well I assume more than just physically having O2 sensors, it's the difference between closed loop and open loop. In systems without O2 sensors it's always OL, so you can set the desired fueling and that's pretty much it.
In a CL system (with O2 sensors) there's only so much tuning you can do as it will tend to "learn away" any changes in its attempt to get back to factory spec'd AFR. In cruise conditions (arguably where the most fuel economy stands to be gained) a CL system will always utilize the O2 sensors, and will only use the fueling tables without input from the O2 sensors at WOT.
In a CL system (with O2 sensors) there's only so much tuning you can do as it will tend to "learn away" any changes in its attempt to get back to factory spec'd AFR. In cruise conditions (arguably where the most fuel economy stands to be gained) a CL system will always utilize the O2 sensors, and will only use the fueling tables without input from the O2 sensors at WOT.