Great thread man, I've got so many suggestions, I could go on all day! I'll try to limit it...
Obviously seeing each of the game player characters more in-depth would've been great. Leaf, Gold/ Ethan/ Jimmy, Crystal/ Kris/ Marina, Brendan, Lucas, Hilbert, Hilda, Nate and Rosa appearing more, as recurring characters/ friends/ companions/ rivals would've been great. I'll always be gutted about that. Silver appearing as a recurring character/ rival would've been especially good and made the Johto series much better. I'd have always enjoyed seeing Wally as well, as a recurring character or more friendly rival. Maybe Yellow and Emerald from the manga as well.
Orre and it's characters would've been amazing as a one-off/ mini series. I'm surprised we didn't see Benga at all, same with the Shadow Triad. Disappointed we didn't see Yancy/ Curtis as well, they could've at least apeared as one offs. I guess most of the Unova series seems a bit of a missed opportunity/ disappointment to me.
Perhaps a more minor one, but I remember during the first UK run of the original series, I was genuinely surprised and disappointed that we saw no Mr. Fuji at all. Obviously now I can appreciate that whole story was probably a bit too dark/ heavy for the anime, but still. Also, I've always maintained that if they'd given Ash a Clefairy, as well as Pikachu, that would've been great, à la Isamu Akai's Clefairy. It's personality is so different to any other Clefairy we've seen in the anime and it would've been a great counterpart to the largely goody-goody Pikachu. I could've seen it and Pikachu being rivals. It would've made some great scenes in the original series, with it perhaps being dropped for something else at the end of Kanto, or in Johto.