My post may contain spoilers of System Shock (SS1) and System Shock 2 (SS2).
I think it would be an interesting approach to, instead of building SS3’s plot on the simple idea of destroying SHODAN permanently, consider the possibility of the protagonist restoring SHODAN’s moral constraints, undoing the damage the Hacker did to her personality. I find that this allows for the exploration of new and different gameplay, conflict and story directions, thus making it in my view a more interesting objective than just destroying SHODAN (again). I think it would be particularly interesting how would SHODAN look at the misery she has created (which I think is actually downplayed in both games) after she had her morality re-fitted. It might lead to an interesting plot closing. It might even kill her.
Additionally, it is my opinion that SHODAN is in a very precarious situation given how massive her failures have been on the two games. Given the time that has elapsed since her creation, it is reasonable to assume (even if taking into account her refactoring her own code) that her internal structure is also approaching obsoletion given the current (game time setting) speed of technology development (even if she, unlike Xerxes, uses relatively few processing power in safety protocols). Even for someone with an ego as massive as hers, her impressive shortcomings (from creator of life to a data wafer; from architect of the universe to a cibernetic implant) and her rapid aging should be taking a considerable toll on how she views things. Even the mere fact that she resorted to creating a backup of her in SS2 (in a human, no less) hints that her ego may not be as large as she likes to show, think or give the impression of. It is also possible that SHODAN is struggling with internal data corruption (which may be spreading) due to the Hacker’s meddling with her systems. There are audio samples where I think she seems to be genuinely struggling with her speech synthesis (and not just trying to sound ominous).
I think it is not particularly impressive to destroy something that, despite how boastful she is, seems so down on her knees, so close to both self-destruction and a major psychological crysis. What would she amount to, being practically single-handedly defeated by a relatively unexperienced human, twice, even with the backup of an entire army of cyborgs (SS1) and able to alter reality itself (SS2)? If she can analyse historical data and extrapolate from that probabilities with two decimal places, I think she can realise just how bad she performed from hard data alone (massive ego, or not) and the discrepancy between how good the data tells her she is and how good she thinks she is. That alone could be enough to put her in an irrecoverable self-esteem crysis.