It's certainly an interesting conundrum. Is this maybe one reason why we see so few high-res 2D games on modern hardware? I always thought this was down to 2D simply being out of fashion, but it seems as though video hardware has a natural dislike for large 2D images, as opposed to complex 3D models, which they seem to handle fairly easily.
I've been playing around, and loading the textures, one for forground and one for background, straight in as one object takes up 16mb VRAM. Chopping these up into 512x512 tiles and tiling them drops the count to 12mb. Cutting them up further into 256x256 tiles and minimising empty space drops it to 11.25mb, but the difference seems negligable at this point.
For this project I've always intended to allow different graphics settings so most people can at least play the game, however, this VRAM issue is quite a large one. I intended for low graphics settings to disable certain visual effects to improve performance; however, Construct seems to be able to render plenty of effect with little performance drain. Disabling these effects will compensate for cards with old pixel shader versions, but won't affect VRAM usage much at all.
With 3D games, as you say, they can just whack the resolution and texture-quality right down to allow them to run on older machines. However, they aren't designed with this setting in mind; the games are designed in high-resolution, then simply scaled down if needed. They are effectively designed with mid-high range graphics in mind. I can't do this with a 2D game; artwork is artwork, it'll take up the same space regardless of how crappy it looks, and scaling it down to fit lower resolutions won't work. Thus, I have to design the game with low-range graphics in mind, and then scale it UP if someone has a decent rig.
Taking into account low-range cards at around 64mb, what's the largest amount of VRAM I can afford to use? About 32mb? Does VRAM refresh for individual layouts? If so, with backgrounds using ~12mb per screen, I could get away with using high-res textures providing I use individual layouts for every screen of the game. Doing so would be a logisitcal pain in the ass, but should keep the VRAM of each layout down to a usable amount.