What Karen and "friends" did to Penny was high-school politics, yes. And from Penny's clearly thought-out, wise motivational speech to Aggie, it's clear that while Karen had hurt her, it wasn't a fraction as much as she'd hoped to do. Karen presumably wanted Penny to turn into something like Pathetic "I got...projects" Penny, or in her own frame of reference, the "Old Me" with the ugly hair, stained, schlubby clothes and fatalistic, passive attitude. Instead she ended up producing Heroic Penny.
What Karen did to Aggie was...well, she said rather nasty things when Aggie was already down, but she couldn't see Aggie crying on the sidewalk, and she had just heard what happened from Marshall's anger-distorted perspective. And Karen was herself crying as she told Aggie off, suggesting that, unlike the calculated way in which she and the IG stole the spotlight from Penny and manipulated her friends away from her one by one, Karen was speaking to Aggie out of her own pain. Maybe not a fully justified pain; I doubt that Aggie, even if she'd continued stifling herself from "true love confessions" in Marshall's presence and continued biding her time, would ever have succeeded in luring him away. But a genuine pain nonetheless, producing a response that happened, along with Marshall's majorly disproportionate and downright mean reaction, to make Aggie think she couldn't go on. And in any case Aggie, with Penny's help, was able to, as she put it, "keep moving" nonetheless.
Really, the worst thing the IG did, in terms of both intent, potential result, and actual result, was what they did to Sara and Michelle. And although Karen bore some responsibility as the leader of the IG, neither the rape video/poster campaign nor Michelle's eating disorder were her doing. (Although Karen had advised Stan to get Michelle to dump her by ordering a "diet salad with the emphasis on diet," Stan didn't take that advice, and Cyndi...well, we now know she had entirely her own, deliberately lethal motivation.) Indeed, when Helen drunkenly said what she said and Karen called an emergency IG meeting, she didn't care about Sara's lesbianism, but about Aggie possibly stealing Marshall away. It was the others, led by Meg, who said "Forget Aggie; let's ruin Sara's life so she too will abandon Penny." The upshot is that it was what they did to Sara and Michelle that had to be stopped, before they did it to others. Because had they done it to others--as indeed they (minus Meg) subsequently planned to do to Duane--there could have been far more widespread and tragic consequences than what happened to Penny or Aggie. So even if her choice of words--"That's what she'll do to the world"--may strike some as overblown, Penny was 100% absolutely positively correct that Karen and her allies had to be stopped.
As for Cyndi subsequently going on to be a worse threat...well yeah, she was, but as T said here recently, she wasn't the sort of threat Penny, Aggie, Stan and friends could've done much about. And not for lack of trying: Stan telling Cyndi off in "Out Front" only made things worse, and Penny sending the audio portion of her "blackmail" video to Carl in "Mister Smiles" did very little (it made Trisha marginally more suspicious of her daughter, but that was it). No, Cyndi was really a unique case. And that, as T said, is why ultimately her undoing had to come from someone whose actions she couldn't have predicted, because she too was disturbed in her own way, and as an indirect result of that, from Cyndi's own journal.
"Life doesn't wait forever." --Lisa Winklemeyer