I think the biggest mistake Marvel ever made was ditching the format of the comics actually happening in real time. In the early Marvel days, up through the 80's, the stories actually occurred in the years they were set, and the characters grew and evolved. Peter Parker started as a High School student, but eventually went to college, got a full-time job, got married, etc. At some point they decided to adopt the "sliding time scale" and it was fine for a bit, but when you're going DECADES with these characters and they're permanently stuck in their thirties, it just gets convoluted. If they'd stuck to the original format, they could have introduced new characters as time went on, with Legacy heroes becoming the norm. You could have Peter Parker growing older, no longer active as Spider-Man, but mentoring the new hero to wear the mantle.
I know some readers wouldn't like this, as "their" Spider-Man or Captain America would always be the original, but I also think it would give new generations a chance to have their own characters to attach to. There are plenty of people who grew up with Wally West and Kyle Rayner being "their" Flash and GL, and if Barry and Hal had still been in the books guiding those new heroes I think there would have been a greater acceptance of the new guys by older readers.
Now it seems that both of the Big Two have to either do a "soft" reboot or a full on "Crisis" style revamp every few years because the continuity gets so bloated and confusing. One writer chooses to bring some element in from the previous continuity that another writer ignored, and the whole cycle starts anew.