Ditko's departure affected the series in every way you can imagine... not all of them bad, BTW. MJ's first appearance would have never had that knockout quality it had if Ditko had done it and characters like the Kingpin would have never shown up, most likely. Steve was also getting more and more into his "A is A" Ayn Rand Objectivism deal which would have put a severe slant on future Spidey stories. As John Romita said, Steve was writing stories that were hard on beatniks. I doubt he'd have wanted Pete to get a motorcycle, grow his hair out, and sympathize with protest rallies. All of which put Ditko far enough out of the Counterculture that it is probably just as well that he wasn't in control of Spidey in the late 60s.

On the other hand, Steve always felt that Peter should stay miserable and I rather agree with that. This business of suddenly being surrounded by gorgeous Romita babes does take the edge off a lot of what Spidey should be about. Marrying MJ and making her a supermodel makes the whole thing a hundred times worse, of course.

There's no doubt in my mind that Ditko is the best artist for drawing Spidey in those wonderful, eerie spider poses and those great action sequences so that gets lost when he leaves. Those wonderful gang war stories are never the same after he's gone. And look at the villains Ditko created (Chameleon, Vulture, Ock, Sandman, Lizard, Electro, Enforcers, Mysterio, Green Goblin, Kraven, Scorpion, Spider-Slayer, Molten Man, etc.) compared to how many new villains appear in the rest of Stan's run (Rhino, Shocker, Kingpin, Man Mountain Marko, Silvermane, Schemer, Gibbon... that's about it). I'm sure there would be plenty more odd, classic Spidey villains if Steve had stayed around. Also, we lose the distinctive pacing and plot flow of the series as laid out by Ditko.

Finally, we lost all of Steve's subplots. Norman Osborn would have never been the Green Goblin... which would be a good thing. The whole Norman-then-amnesia-now-Lex-Luthor-clone could have been avoided. And it would have been nice to find out what Steve was really planning with Norman and with Betty and with Mary Jane.

It's not a tragedy that Ditko left. Romita is great. Stan did some wonderful stories. And you can get a sense of where Steve may have gone by looking at his subsequent DC and Charlton work. But for an old Ditko buff like me it's hard to look back at these things and not wonder what might have been.