While the changes made to this show from its source material have gone over well with some fans, they haven't gone over well with others to the point where the show might as well be called They Changed It, Now It Sucks: The Series.
- Grandpa Lou’s Adaptational Personality Change from a sharp-witted Grumpy Old Man to a calm New-Age Retro Hippie didn’t go over well with fans of the original series.
- Some weren't happy with Betty being a single lesbian mom since it meant cutting her husband Howard out of the series in the process (although the creators have hinted he may make an appearance in the future). Others felt like it fell into stereotyping to write the most masculine and outwardly feminist mother of the group as a Butch Lesbian.
- The fans were not exactly thrilled that all of the grown-ups were recast (notably Stu and Grandpa Lou, with many people saying Lou in particular barely sounds like the original). While some fans were more forgiving since some of the adults' original voice actors had passed away or retired between the end of the previous series and the start of the new one, other fans couldn't get past how Kath Soucie reprised her role as Phil and Lil in this series, but not her role as Betty.note
- Kimi and Susie's ages essentially being switched caused some discomfort to longtime fans of the originals, especially since Susie now being younger than Angelica means she's a subordinate rather than someone who can put Angelica in her place. Kimi being introduced differently than in the original show caused a divisive reaction since people got the impression that her mother's relations with Chas and Chuckie were Adapted Out; which would have meant a core element of her role in the original show, Chuckie gaining a stepmother and little sister, was gone.
- In general, many weren't happy about the show being set in an Alternate Continuity and being computer generated instead of being set in the same continuity as the original (during the events of the original and before All Grown Up!) and using the same animation style.
- Fans felt like the new Boris and Minka might as well be completely new characters due to their designs being drastically different from the ones in the original cartoon, with Minka, in particular, looking more like Aunt Miriam.
- Drew has more of a friendly rapport with Stu in contrast to the hot and cold relationship they had in the original series. Of the interactions between the adult characters, fans consider Stu and Drew to have some of the funniest moments, usually because both act like children when they fight. Even All Grown Up! shows they haven't completely buried the hatchet.
- Dil's design was met with a lot of scorn for being overly ugly when first revealed. While this has calmed down with later episodes showing his head slowly changing shape and face losing some of the wrinkles that made him so unappealing, others still argue that he was made far too ugly.
- Due to them keeping Dil far younger, to the point that he can barely move in some episodes, and being completely unable to talk, people have complained that Dil is even more of The Load than he was before.
- The remake of the original theme song got a fair amount of criticism due to the synth sounding somewhat broken with some finding it outright painful to listen to.
