Penny and Aggie/WMG

Penny and Aggie "experimented" with one another sometime before the series began.
The Word of God is that there's a yet-unrevealed reason for their petty rivalry. Sara's theory that there was a lesbian attraction between the two struck a nerve on Penny, compared to her blasÃ© reaction when Sara herself came out; the self-consciously gay-friendly Aggie has a similar reaction when Lisa suggests the same thing. In an early internal monologue about her sexual preference, Aggie wonders whether she "prefers," not "likes," girls. Could it be that their apparent insecurities were fear of being outed? Could it be that Aggie's decision to "never speak of that possibility again" was driven by her past mistake with Penny? Could it be that that night set off the whole rivalry? Could it be that this contributor is just looking to justify a ridiculous pet theory?
 * Then again, Aggie seems pretty flustered when the subject comes up...
 * Effectively Jossed by the fact that both girls, in the "May" and "June" chapters, consistently behave as though so much as kissing each other (or indeed kissing anyone, in Aggie's case, or kissing a girl, in Penny's case) is completely new to them, and more than a little scary.
 * The reason for the rivalry was revealed in "What you can't teach." And what's shown there still has an impact on the strip, even as it's now heading into the last few weeks of strips.

Meg and Helen are sisters.
There's very little evidence to suggest this--in fact, the only time we've seen Helen's family is in this strip. But the things we do know about Helen's sister--namely, that she's older, blonde, and accustomed to being lavished with attention--all apply to Meg. It would also explain why Penny felt so comfortable with taking Meg down--her "poaching" of Braz was more likely a "last straw" kind of situation and less of a first offense. The theory may be Jossed here, but it's also possible that like Daria and Quinn, the more popular one has disavowed any relationship to the outcast.
 * The August 23 2010 strip of Something Positive showed that Helen at least called her sister to let her know she's okay. That doesn't sound like a bad sibling relationship.
 * Probably Jossed. Meg's last name is Macomb.
 * Word of God says Helen's sister is named Summer.

There'll be a crossover with Ménage à 3
Proof? Remember that filler week about the Korean family? And Junghien, Zii's boss, is Korean. A bit far-fetched, but hey, this is WMG!
 * Well, Ritch and his buddies made a cameo appearance as three gay porn stars in one page. So... I think this is already a closed case.
 * Even though this is a Just for Fun sort of page, I feel I should mention that those gay porn stars, as T Campbell pointed out in the P&A forum, are not Rich, Stan and Jack, but lookalikes that Gisèle Lagacé drew into that Ma3 strip as a last-minute joke. Although Lagacé, as founding artist of P&A, does have part ownership of those characters, Campbell was understandably miffed at this "joke," as he's since had to explain to more than a few readers that no, the canonical Rich, Stan and Jack did not make a porn video. Source for T's statement here.
 * I haven't read that strip (and I thought I had all of them...), or removed it from my memory. But since Word of God says that they aren't, it doesn't count. (Maybe P&A exists in the MA 3 'verse, and they made a porn parody of it?

Rich, Stan, and Jack all have identical twins.
And their twins are all gay, and they all moved to Canada to star in gay pornography in Ménage à 3

Since Gisèle pointed out...

 * ...that both Penny and Aggie are based on two conflicting sides of her own personality as a teenager: The whole comic is about her coming to terms with herself. Put a completely different light on their eventual lesbian relationship, doesn't it?