What do you mean by redo the math?
well you don't want to use the default character sheet and have 400x400 events. that would make the sheet over 6000 pixels in size. You really want to stay below 4096 IMO. Most systems can use those fine, I know a lot of intel graphic cards can support 8192 textures now, but it makes me cringe to think of having the image so big really.
Because of this, I think you would want to use the smaller character sheet, that is just a single character per event. That would keep the image at 1600 pixels in size.
The script does not respect single sheets, so the math would have to be redone. I can't recall if I tried using a super huge 6000 pixel image or not, just seems wrong. Sure it would work on my computers, not sure it would work on everyone elses.
The script only steps through a sprite sheet as if its the default one, so I opened this a while back
And yes, I think 900 is the limit of tiles you can get away with. But just use multiple rooms and smart transitions and its not an issue.
The actual size of your textures shouldn't be an issue.
For some stuff you just need to get creative. You can't change the textures on walls in the rooms. So design around that. If someone pushes a button and should open a door, either push them through it, or give them an updated message. If something like a button is in the texture, but is no longer usable, change the event to tell them "can't use this anymore".
For example, if there is an axe laying on the ground, don't bake it into the texture. Instead have like a grove or crack or something noticeable like a lever in the texture. Let the player interact with that, tell them it pushed some stones out of the way and behind it you found an axe. That way no need to change the texture. And if they try to use it again, tell them, nothing else to see here ^_^.