The one big difference between the Powerpuff Girls and the Rowdyruff Boys are their weaknesses. Though the Powerpuff Girls have been defeated before, they don't have any glaring weaknesses except when they are divided. The Rowdyruff Boys, on the other hand, have several significant weaknesses that they all share. Due to the boys' being having higher tolerance for damage than the girls, they are almost impossible to defeat in head-on combat, this is proven in their first encounter where they were the only ones that could defeat the Powerpuff girls in a fair fight, these weaknesses must constantly be exploited by the Powerpuff Girls.

* Girl Kisses/Cooties: While they have superpowers, the Rowdyruff Boys are still little boys and fear girly kisses due to cooties. This is the reason why they are defeated in The Rowdyruff Boys. After the Powerpuff Girls regain consciousness following their defeat at the hands of the boys, Ms. Bellum tells them that there is one thing all boys hate, hinting at their weakness. Heeding Ms. Bellum's advice, the girls each land a kiss on the boys, causing them to explode. Ever since their revival in "The Boys are Back in Town", they have become immune to girly kisses thanks to Him's anti-cootie vaccination.
* Love of Destruction: In the episode "Boys Toys", the Powerpuff Girls agree to form an alliance with Princess to use use her weapns to defeat the Rowdyruff Boys. The girls don't actually cause any harm to the boys even though they aim their weapons at them, (a tank, plane and boat.) The boys are awed at how much destruction the weapons cause and soon take advantage of each of them. The boys aim the weapons at each other and end up enjoying playing with them so much that their own laughter subdued them.
* Individuality: If the boys or girls are separated, they are easily defeated. This is shown when Boomer is ordered by Brick to get sweets. The Powerpuff Girls spot him after stealing sweets from another boy and the three girls easily defeat Boomer. His injuries included a black eye, missing teeth and torn clothes.Yeah, I know. I'm kind of, uh...
* Femininity: While all the boys only take pride in being tough and aggressive, they hate anything considered "girly". When Bubbles was disguised as Boomer, Brick and Butch were spray painting graffitti on a wall, Brick caught sight of Bubbles painting the words "flowers are pretty." As soon as she caught Brick and Butch's furious looks, she added the word "dumb" underneath. Boomer also gets makeup put on him in the girls' attempts to shrink the boys down to their original size. Boomer shrinks with embarrassment as Brick and Butch find it hilarious
* Embarressment: While Him's cootie vaccinations made the girl's kiss's ineffective against the boys and actually made them more powerful. The boys will shrink in size when humiliated. Such as getting wedgies, makeup put on, etc. They can become several times smaller than their original size and break down crying if they are embarressed enough. And my brothers call me a wimp!Oh wait, this is about me too...