How distinct is each playthrough?

[10 points for apathy]

It's been a while since I've completed the first ending and I'm wanting to return, but I'm worried that I may get a bit lost. I'm not often one to replay games from the start and am hoping that I can just pick up where I left off.

[TheSeek]

What you played is route A and you got ending A, loading the same save you'll play Route B, which is the same events of Route A but from a different perspective. This means that while some sections will be more or less identical(even if with a different approach to combat), there will also be quite a few different sections, I'd say half of Route B is new gameplay section(still in the same events as Route A).
During this route, do not skip cutscenes even if you think you've saw them already, some of them will have added details and some extra parts.
Once you're done with Route B with ending B, you'll load the same file again and play Route C, which is 100% new content story wise and is the continuation of Routes A and B. Route C will lead to endings C or D depending on a final choice. Once you completed Route C once, you'll unlock chapter select, which you'll have to use to go to the last chapter of Route C to change that final choice and get the other ending C or D you didn't get the first time. Now that you have both endings C and D, something different will happen during the credits and you'll be able to get ending E, which is the true ending.
All of this, getting endings A to E, is ONE playthrough.
Before you ask(and i don't mean you will ask, but some did so i'll play safe), none of this can be skipped, and even if the prospect of repeating the same events of Route A in B sounds disheartening, it contains pretty much the most important information in the whole game...in a way, Route A it's only the introduction to the context of the game, the real game and story only start in Route B(it's not a coincidence that the titlecard for the game, being when the game title appears during the game itself, only appears at the start of Route B).

As an advice, do most side quests before finishing Route B, they'll provide a lot of information, lore, and worldbuilding to help better understand the story, and it's not an exaggeration to say that some of the later events in the game will seemingly be out of nowhere without the information you get in some side quests.
Also, for the same reasons, do most if not all side quests(the ones regarding completing stuff like fishing and gathering enemy data can be skipped) in Route C.

You do you of course, but if you don't remember anything of Route A, i'd still suggest starting it all over and playing Route A again, some of the tiniest details you might not remember are what make this game a good game and what will help you to connect the dots.

[10 points for apathy]

<3