
I would argue that you don't know how a particular plot point is going to end, even if you are devour every piece of material about what goes on behind-the-scenes at Marvel. One More Day didn't change a thing in terms of whether Spidey can get married in the future. With the sliding timescale, a fictional relationship could theoretically last for over a decade's worth of printed comics. And at the end of that decade, there may be an entirely different editorial philosophy.
A particular fictional relationship probably won't last for a decade's worth of printed comics. But that has nothing to do with OMD, and everything to do with what the writers naturally want, which is to shake things up every now and then in the romantic department. While any new development is more likely to be temporary than it is to be permanent, you don't know for sure that it will fail. It's entirely possible that a new dynamic so successful that it changes the "rules" of a franchise. Spider-Man and Wolverine have been on the Avengers for more than sixty issues. Bucky's been back for almost as long. Bruce Wayne's son is the new Robin. Matt Murdock's identity as Daredevil is essentially an open secret.
Readers certainly don't know what's going to happen in the short term. Peter Parker may still be in the same relationship an issue later, an arc later or an year later. If written well, you can appreciate the journey as opposed to the destination. You can enjoy the Avengers, even if you know the team probably won't be the same at the end of the year. You can enjoy a fight scene between Spider-Man and Dr Octopus, even if you are reasonably certain that neither's going to die. The B-plots are often more consequential than the A-plots.
Even if you assume that a relationship is going to come to an end, you don't know how exactly that happens, or how that changes the status quo. A story that ends in heartbreak is contrary from one that ends in an amiable parting of the ways. And the ramifications will differ as well.
It could still be consequential for the characters. The relationship will become part of their backstory. Because Carlie Cooper dated Peter Parker and now knows his secret identity, she is going to be a different cop buddy for Spider-Man than Lamont, Jean Dewolfe or George Stacy. It's not something Batman and Commissioner Gordon have had to deal with.

Mark Waid is pulling this off in Daredevil, with the man without fear embracing his swashbuckler persona in the aftermath of a demonic possession and multiple tragedies. In that title, Matt Murdock is currently involved with the Black Cat, who has been hired to steal something from him. The relationship is probably going to end badly, but there's a significant chance that it will be consequential for Daredevil, the Black Cat and Spider-Man. It's something that could easily be referenced decades from now.
A final point is that the most likely alternative to the One More Day retcon would have been a situation in which Peter and Mary Jane stayed married, with a fairly constant quo. They wouldn't get older and they wouldn't have kids. I get the impression that it would take longer for the average reader to realize that a single Spider‑Man isn't going anywhere that savvy readers would have realized that an eternally married and childless Spider‑Man isn't going anywhere. It would take them slightly longer to realize that post-OMD, just because there's more variety possible with a bachelor Spider-Man, as his relationships are more prone to change. Plus, readers are aware that once upon a time, Marvel did actually allow Spider-Man get married.
A complimentary argument to all of this is in addition to "knowing" that every romantic relationship is doomed to failure, the readers also "know" that Peter and MJ will be reunited at some point in the future.