You know Steve Ditko planned to kill off Betty in his run. Blake Bell's biography of Ditko mentions that. Ditko wanted to kill off Betty in a domestic accident (falling down the stairs) rather than someone criminal. Lee nixed that idea because he felt it would give too much baggage to Peter at that stage and Ditko actually said that Lee was right.
Stan Lee was generally not a good writer of romance and relationships. Susan Storm, "first lady of the Marvel Universe" has never actually lived up to that title in anything outside of a token sense. And the Reed-Susan relationship is the main hurdle people face in adapting the Four, since they are bland characters and their romance is bland as hell (I do like how Hickman wrote them though). Mary Jane is easily the best female character that Lee wrote and that's mostly by accident rather than design. In fact I think that once Spider-Man became a big title, Lee decided on giving Spider-Man a permanent love interest to make his titles resemble or come more in line with Daredevil, Iron Man and FF.
In general, most of the Silver Age love interests (Karen Page, Pepper Potts, Betty Ross) were added in because it was part of the convention and not enough work was done to make them work. And eventually all kinds of horrid stuff happened to them. Pepper Potts got the best of the lot. It's difficult to say if Karen Page got a worse deal than Betty. The latter at least is still alive (and pretty interesting in Immortal Hulk -- "This is me") but that was after a period where she died multiple times and on one occassion got raped by Nightmare (the Dr. Strange villain). Karen Page got to die in a mediocre Daredevil story after being a major character in the greatest Daredevil story of all time (which admittedly didn't do favors for her). Especially now that Deborah Ann Woll's turned heads in the Netflix show, Guardian Devil has revealed itself to be the big mistake it always was. Pepper Potts (who is clearly the first lady of the MCU in a way Susan Storm never was in the comics) owes her prominence to Gwyneth Paltrow and RDJ insisting that they make Tony and Pepper settle down since he didn't like being playboy Tony.
You know, I'm not a fan of "they didn't know how successful the character would be" school of retconning and overwriting continuity...but that argument cuts the other way. X wouldn't have aged Peter out of high school had they known how successful the character would be...at the same time, knowing how successful and iconic the Peter/MJ romance became, I am pretty sure that Lee and Ditko and others wouldn't have wasted people's time with Betty, Liz, and Gwen. I mean that's what inspired Bendis to use Mary Jane as Peter's one-and-only in USM. Everyone knew she was the heroine of the books so why waste people's time with rotating stuff.