Episode 75 is referred to as Stupid Mario Brothers: The Movie 2. Due to its hour length.
Franchise Original Sin: The show can trace a lot of the problems of Seasons 4-5 back to show's highpoints, specifically:
The Darkness. When he was first introduced, in Seasons 3 respectively, he was seen as interesting, intimidating, and all around a villain the audience could Love to Hate. However, that meant that when the storyline moved past him, the writers decided to bring him back, at which point they overexposed him significantly, meaning the audience grew sick of The Darkness.
In Act II of "The Stupid Mario Brothers Movie" The Darkness gets back up off the ground after being seemingly killed by Wario, because of a counter curse that was never hinted at. It didn't screw up the movie's plot, even if it made no sense when you really thought about it, so it was tolerated at the very least. Also, Liquid Snake came back to life with no explanation given (though it's hinted that The Darkness had a role in it), but it worked since it lead to the face off scene between Solid and Liquid Snake. This lead to a major annoyance most fans had in the later seasons, where characters are revived for no reason (no good reasons, at least), simply to provide a villain in the laziest way possible. This even got Lampshaded by Snake when Vercetti came back, indicating that at least some of the cast and crew were sick of it as well.
Many fans found it extremely hard to sympathize with Mario and Luigi in Seasons 4 and 5, seeing as how utterly isolationist they are. Said isolationist thoughts were present in the very first episode, and worked, since the idea was that Mario and Luigi were fed up with having to save the Mushroom Kingdom all the time and decided to have a vacation. In later seasons, Mario and Luigi do little to solve the problem of the beacon's destruction and actually seem to like it better that way.
In Episode 7, after reading Bowser's letter, Mario says (in relation to Bowser's mention of eating a goomba), "Imagine being in Bowser's digestive system!" Coincidentally, one and a half years after this episode was released (which was 2008), the game Mario & Luigi: Bowser's Inside Story was released (in 2009), in which the brothers spend most of the game traversing Bowser's body.
The show's characters are primarily based on Super Smash Bros. and other Nintendo series. However, Capcom character Ryu ended up joining the show several years before he was announced for Super Smash Bros..
One of the major plot points from Episode60 was that the Darkness had survived his death at the hands of Wario by effectively turning his hat into a Soul Jar and then getting rid of it; he later transferred himself into Ness's head when Ness put on the hat in the "Operation Blind Storm" special. Flash forward to 2017, and we get a game in which Mario can effectively do the exact same thing!
Ash and Brock (and when Ash left, it became Brock and Gary)
Hype Backlash: Season 5 to an extent. It left Richard really upset as he believed he had wrote the best season ever for the finale and having read the negative reviews really bought him down. It thankfully died down with episode 75 which fixed up most of the season's problems and delivered a truly great ending.
I Knew It!: Wario being the second Chosen One was one of the main theories of the fans.
Narm: The blood effects used in one of the later season 3 episodes may come off as a childishly gratuitous attempt at Darker and Edgier. The creators may have realized this, because for some reason future fight scenes lack this effect.
Then in the finale, it is revealed Mario was significantly weaker during that fight.