It's a matter of tonal and narrative consistency - you can have a wacky, off-the-wall, comedy where crazy, nonsensical stuff happens all the time and it works... or you can have a funny, but down-to-earth sitcom where even the occasionally more outlandish stuff fits with the rest of the tone and it works...
... but when you try to do both it's usually a mess, like Family Guy where we're expected to take the death of a main character as a serious, heart-wrenching moment 5 minutes after a wacky action scene where they escape a horde of alternate timeline indians. It's the Loss Effect.
Proud Family suffered from the same problem - some episodes are completely crazy, others are serious and dramatic, and others bounce from one to the other over the course of 20 minutes. It's hard to take an episode about violence and discrimination against Muslims in post-9/11 America seriously when it's the follow-up to a Dr Doolittle parody where Penny learns she can talk to tigers, and it's hard to enjoy a weird episode with an Al Roker genie when you're still feeling super uncomfortable after the A Very Special Episode About Kwanza with the depressing Little Match Girl homeless family.