I think the intent in the original series was that Starfleet couldn't go into primitive cultures and mess with them.
Except that by using the judgmental word "primitive," you're playing into the very ethnocentric and colonialist assumptions that the PD is supposed to caution us against. The PD is about recognizing that it's wrong to define other cultures as "primitive" or inferior just because they have less technology -- that they are still just as capable of thinking for themselves and are better-qualified than you are to understand their own societies and find the right solutions to their problems.
This is why the 24th-century take on it in "Pen Pals" and especially "Homeward" is so ugly -- because it's forgotten that the PD is about respect for other cultures' equality and independence and has fallen back into the colonialist mentality of "They're too primitive and childish to think for themselves and so we have to make the decisions about their fate without giving them a say in the matter."
So I don't know how Picard works that out, given his absolute interpretation of the Prime Directive in Pen Pals, and the mis-interpretation of it in I Borg. When Picard had the chance to wipe out the Borg, he should taken the shot and infected them with the virus that Data and Geordi created.
Huh? That had nothing to do with the Prime Directive. That was about basic decency, about recognizing that Borg drones were victims rather than monsters and that it would be immoral to exterminate them.
Moreover, people keep forgetting that he did
infect them with a disruptive meme: Hugh's individuality. The effect was the same: an entire population of drones was neutralized, taken away from the Collective. (Presumably whatever failsafes intervened to protect the rest of the Collective from the individuality meme would've been equally effective against the destructive program, and neither would've spread any farther.) It's just that they were liberated to think for themselves rather than mass-murdered.
The example Gene used, was the Spanish Missionaries and how they would go into an area and try to turn the local population into citizens of Spain, teach them a new religion, etc. It is judgmental. They do use the word primitive in their definition.
And what did Picard get for his bad decision...a bunch of rogue borg that still murdered colonists because they fell in with Lore. They also had the collective to deal with. If you are going to fight a war, you fight to win you don't drag it out. Like Kirk's definition of War in a Taste of Armageddon. Picard was looking for a clean solution, and war is never clean.