OK, so Edmund has said "this is it for Isaac" basically. No more expansions, endings, or whatever. We can assume he's going to hold his word on it this time, as he's not about to get another remake made.
BUT, we know that there is another Isaac-themed game coming out - The Legend of Bumbo - which looks like it's swapping the top-down Zelda gameplay for 1st person RPG mechanics.
So keeping that in mind, let's consider the two new endings:
1. Greedier Mode's ending is pretty much just Greed Mode's ending.
2. The Void ending is the final confirmation of what the community deduced from all the other endings. We now know that the story is something like this:
Isaac's parents split up after arguing.
Isaac is saddened by this. But for a while, things are OK (notice the clothed Isaac picture with Mom - they both seem pretty cheery)
We know Mom is not happy due to the shot of her crying, though.
Isaac begins dressing up - one drawing is of him wearing the Maggie wig.
The drawings on the left are the supposedly on the nose ones, which so far have been interpreted as just Edmund being VERY BLUNT.
The ending thus goes, if you follow common logic:
Bad stuff happens. Guppy dies, Mom begins to treat Isaac badly, probably due to her own grief or her fear of him dressing up as a girl (one of the new between-floor cutscenes of Isaac walking around in a dress). We know some of the abuse is real, not imagined - he is inside his room naked, after all.
Isaac begins to see himself as evil/cursed/sinful.
Eventually, he begins contemplaying suicide, and goes through with it, suffocating and rotting to a skeleton within the toy box before Mom eventually finds his remains.
THE END. Right?
But there are a number of open questions.
1. Why was the toybox filled with photos? Why was one burnt? Was it Isaac or Mom that did that?
2. Is there a reason that Isaac's parents argued and split? We know it's not due to the death of Maggie now - she never existed.
3. What's the deal with the weird Greed endings - especially the new one, which makes no sense to add now the ARG is over?
and most importantly:
4. Why does Isaac think he's the DEVIL?
Not just evil or sinful. Isaac literally thinks he is Satan.
Consider the grey landscape that Isaac wakes up in after his death. It's not in the game itself, and we've seen it twice now, in endings 17 and 20.
Now consider two things regarding Isaac's shadow. In ending 17, we see it pool behind him and form a devil-like shape. In the Chest ending, though, we see something interesting too - a polaroid (read: not a drawing) of Isaac with a dark shadow behind him.
So. We have Isaac walking a barren grey landscape which is unexplained (is it limbo?) and this Satan/shadow thing that I think is still not very well explained.
So here's a what if:
What if the current understanding - of everything being in Isaac's head - was actually false?
Suppose Isaac - the real Isaac we see in the harder to find endings - actually was haunted by an evil spirit? What if that polaroid was actually showing reality?
If this was true, it answers the Satan question, and potentially answers the reasons for Isaac's abuse and Dad leaving. Isaac becomes haunted by a dark spirit. Dad leaves, understandably unable to deal with it. Mom attempts to deal with it, before growing increasingly abusive. Isaac eventually tries to fix everything by taking his own life. But as we can see from the two endings that show the grey world, this doesn't work. The dark spirit continues to haunt Isaac, and Isaac now wanders alone there - that's the meaning of the final shot of ending 20.
So this leads me to Legend of Bumbo:
I have a suspicion that we'll see Isaac's story continue in that game, or at the very least the story will be referenced and explained more. There are still quite a few questions I'd like answered, personally.