Great thread and question. I think this is kind of a situational thing, with many factors at play, though. You have to consider that not every game is revisited for the impact that a first playthrough may have delivered. Sometimes I revisit games just because they're fun. I do think this is a valid point, and I can attest to the fact that things hit a lot different in a first playthrough. I'd love to single out Breath of the Wild as being a game that just sort of loses something in following playthroughs.
So yes, I'd say a first blind playthrough will most-likely always be the most meaningful, because it's when everything unravels to you, with no expectations there to dull the impact. But while you can never play a game for the first time twice, I'd say in the case of a lot of games, a second playthrough has its own incredible degree of impact, because now you have some context, and you may pick up on new things. It's experiencing the same game through a new lens, and you're still collecting new experiences in doing so.
For some games, that "second playthrough lens" can self-perpetuate and you can keep finding new things keeping the story very much alive many, many playthroughs later. But I don't think this is an incredibly common phenomenon, as probably most games' stories are straight forward enough for this momentum to die after a few playthroughs--but there certainly are a handful of games with stories out there that do seem to do this. I think the less direct and more ambiguous the story/telling is, the more likely for this to occur. But, likewise there are games whose actual gameplay and progression yield this same effect, so the appeal of playthroughs may be less an impact of the narrative but just the immersion you feel on the gameplay side of things. Non-linearity, open-worldness, ability to sequence break... things stay fresh for many playthroughs.
Now as far as either these experiences--story or gameplay--dulling with repetition goes, I think it depends a lot on both the game and the player; why they're revisiting the game, and what the game itself has done for them in past playthroughs. In this way, it probably could be similar to rewatching a movie. Sometimes you rewatch to relive some hype you felt, maybe you rewatch for comfort, familiarity, or maybe you're rewatching to pick up on new things. Or maybe you're stressed or sad or lonely, and turn to it like an old friend. Will the overall film lose its magic as you watch it many times? Again, it's difficult to say, because maybe parts of it will, while others will not. Or maybe you'll associate it with new things, based on things going on with your life when you rewatch, and that somehow keeps it alive in a very different way. Sentimental value is a special thing.
But to close I'll say, there's parts of both films and video games that will give me chills no matter how many times I watch or play them. And I think it comes down to multiple aspects of those mediums' design like synchronizing in a way that makes it resonate very, very deeply. Like, for example, little subtle things like sound design can make your body react in ways you can't really explain. This can create an emotional moment. This can create feedback in gameplay that makes what you're doing extra satisfying. This can create atmosphere, tension, subtextual cues that put you on edge or make you feel good or experience a climatic scene in a more direct way that has you forget you're on the other side of the screen. Maybe for some people, that sort of thing would lose its meaning with time, but for me, it doesn't. I think knowing exactly what creates those scenes helps keep the impact there.
Sometimes just thinking about certain scenes in games, is enough to give me chills. Thinking about what they do, or how they work, it's kind of beyond the game and in my head now. I'll never have the same level of what the **** as a first playthrough, but I think the immense weight of scenes like that will always stick with me, no matter how many times I experience them, or whether I'm experiencing them in a playthrough or just replaying them in my head.
