In the far more streamlined Stranger Things season 1, Mike Wheeler’s (Finn Wolfhard) journey to connect with Eleven (Milly Bobbly Brown) and find Will Byers (Noah Schnapp), alongside Joyce Byers' (Winona Ryder) desperate search to find her missing child proved to be the central lynchpin of the plot. Now, despite significantly less focused seasons in between, the prominence of these characters in the early clips and trailers means that they may be the ones to watch again in terms of narrative pull.
Alongside this, Stranger Things, for many seasons, has had a desperate need to jettison a proportion of its over-bloated cast of characters, and I think this may finally be the one where they'll commit to it. The recurring theme behind the deaths: sacrifice. One of the best ways to keep deaths from feeling cheap is to have the dying character make a sacrifice to save another - think previous seasons’ Bob the Brain, Eddie Munson and even Billy Hargrove.
One of the best ways to keep deaths from feeling cheap is to have the dying character make a sacrifice to save another
At a more specific guess, characters who have already completed narrative arcs may be on the chopping block for those who were still growing when we last saw them in Stranger Things season 4: Steve Harrington may take a bullet for Dustin Henderson, Joyce might sacrifice herself to save Will, Max to help Lucas, and Eleven may even die in order to save Mike. I'm not saying that these deaths necessarily would be satisfying or even good, but they seem to follow established Duffer Brother patterns from previous seasons.
In short, my main predication is that the world of Stranger Things will most likely end in utter carnage, with only a small band of our beloved crew managing to make it through and go out into the world to live ordinary lives.