The only flaw to that program I can think of is, if the flood ever make a return, the subjects would more vulnerable than the other gens (or not).
Not if you put them in Mjolnir armor.
Honestly I feel like the prototype Spartan-IV augmentation process that created Ilsa Zane was so radically different that that should be called Spartan-V. Or that should have been Spartan-IV and what we have now are Spartan-Vs.Nah. The R&D/E portion of the Spartan-IV program would receive more of a Spartan-IV/Beta designation, as the intention of that phase was to test the more... eccentric augmentations before they were mass produced or handed out to larger population groups.
I'm just saying that Ilsa was so different from other Spartan-IVs in terms of strength that she should have been her own class of Spartan. If they ever figure out how to make more soldiers like Ilsa but without the aggression and insanity, then you have your Spartan-Vs.Spartan Vs would be an "improvement" over the baseline S-IV. Physical augmentation performance wouldn't even be the only limit here, I would figure that something like A.I pairing assignments to individuals Spartans, plus -insert whatever GEN iteration of MJOLNIR- would constitute the designation of an S-V. Firepower or max bench-pressing isn't the major concern here (ex. F-22 vs F-35), but how Spartans would use more effective warfighting equipment to overwhelm, eliminate, or target the enemies' supposed advantages and become more effective in term.
The original desire of the Spartan-IV program was to make Spartans who could perform feats done by armored Spartan-IIs and IIIs without the armor.
The differences between the Spartan-II and III programs was not particularly major. Yes, the Spartan-III program had more stable augmentations, but everything else about the program (enhancements and armor) were similar to the IIs but just slightly less good. As for a new armor generation, well, the Mjolnir GEN 2 armor actually came after the Spartan-IV program had begun; there were Spartan-IVs before there was GEN 2 armor, so the two were not developed together. Spartan generations are not tied to armor generations. I would also argue that AI pairings did not change much between Spartan-IIs, IIIs, and IVs, except that a select few GEN 2 armors were developed with internal AIs, but again, that was done separately from the development of the Spartan IV program.
As for effectiveness in battle beyond straight strength, well, if you look at the IIs, IIIs, and IVs, they all fought the same way: with weapons, with their hands, and with vehicles. Some specialized in other areas like Kat and electronics, but those were individual traits, not something brought upon by the augmentations. And increased base strength over the standard Spartan-IV is still a baseline improvement, even it is not a complex one. Besides, we were never made aware of the full extent of Ilsa's augmentations beyond her strength. We have no idea about her resilience, recovery, senses, or dexterity compared to modern Spartan-IVs. I think that the only reason that Ilsa's augmentation type did not get it's own designation is that it ultimately was a failure. Even Project ORION saw several years of success before disbandment (hence why it got its own designation rather than just being referred to as Spartan-II alpha or something).