TLDR: I'm sure I'll enjoy my 1st playthrough no matter what, but for me, the shelf life of the game depends heavily on how much creative flexibility there is in story missions, and how "pick up and play-friendly" activities in the open world are. Each seem at risk, given Rockstar's trajectory.
For me, a big thrill of past GTAs has been the creative chaos. You steal a car on a whim, get in a fight with police, steal their car, sail off a building, bail and run, etc.
In earlier GTAs, this chaos extended to the story missions themselves. Your objective was often as simple as killing one key guy. You could do this the intended way, or you could short circuit the mission by sniping from a distance, taking an alternative entrance, using an unintended shortcut, and so on.
GTA 5 made the story missions more cinematic and character-driven, but sometimes this came at the cost of creativity. You'd often need to hit each key cutscene trigger, beat by beat, to ensure the story advanced appropriately. "Short circuiting" the mission was far less often an option. Still, some of the big heist missions gave a meaningful choice for overall approach, and the sandbox outside of the missions remained very freeform and flexible.
RDR2 narrowed things even further. Much of the main game would follow a similar formula of "ride and chat to designated waypoint, engage in shootout, escape." Very often, the missions wouldn't even let you advance if the stagecoach or key NPC wasn't exactly in the Official Mission Waypoint, making the mission design feel less flexible than ever. (Credit to the youtuber Nakeyjakey for really underscoring this last point, which I hadn't been able to put my finger on quite as directly before seeing his video.)
RDR2 went further still, making a lot of the outside-of-missions exploration weightier and more cumbersome, with stamina, hunger and sleep requirements, and slower (but more realistic) animations for everything, etc.
To be clear, I really enjoyed my one playthrough of RDR2. The slowness appealed to me at first. I had one particularly satisfying 3-hour session where I just explored and hunted and fully engaged with all of the slow-but-realistic mechanics. And of course, there were the funnier missions along the way in the campaign, like the drunken night out, that mixed up the first-time experience.
But the on-rails missions and cumbersome open world activities made my attempt at a 2nd playthrough die pretty quickly. The novelty had worn off, and instead of getting to try an old mission over again with a totally different approach, I was annoyed that I had to do it in exactly the same way...again.
All this is to say that I'm a little worried GTA 6 will be similar to RDR 2 in these ways. The missions in the 26-minute reveal felt very scripted and linear. This isn't the end of the world, and it's probably good that a few missions operate this way for story reasons. But I'll be curious to see how typical it is in the full game.
Similarly, all the open-world friction we're hearing about sounds like it'll be fun at first...but what about at hour 50+? Can't steal certain cars without key tools, cops smart enough to shoot out tires, tracking systems that are hard to shake, a "wanted" system that can leave you permanently on the bad side of the law...
Again, this will probably make things more interesting for the first couple dozen hours. But what about when I want to just pick up and play some GTA for 30 minutes 3 months later? Ultimately, I'm just hoping most of the game, whether story missions or open world shenanigans, has more Hitman DNA than Uncharted DNA. Will be curious where it lands.