I think it's perfectly doable. I'll go ahead and link to the thread for my game Courier. I don't have hundreds of layouts, but I do have a lot, and they're all quite detailed. I have a ton of unique different objects, though I reuse assets as much as possible (note, though, the game is NOT built up of tiles--I wanted more freedom). Land-wise, my game is larger than Ocarina of Time (excluding the dungeons--just everything outside of them). I haven't had any trouble with stuff getting slower because, as far as I know, js will eventually cleanup and drop out unused assets. I've tried to be pretty efficient, however, so my vram use is never very high. The downside to piecing things together like I do is an increase in object count, but I can get a ton more freedom while minimizing the amount of assets I need to create. I rely on some fancier graphics tricks, however, so I don't think a phone version is possible right now (and I'm not interest in mobile anyways), but it's been smooth sailing on PC.
Not as a bragging point, but for comparison: I have more unique NPCs than OoT and LttP combined if I'm not mistaken, my overworld and surrounding areas are bigger than either game's overworld and surrounding areas, every character is animated, grass sways, trees sway, the ocean has waves, etc--it's all very detailed. I have a pretty detailed shadowing system in place. I have maps in excess of 10,000 pixels across. And C2 has run it just fine.
So long as you're careful and put thought into how you design the game, it's perfectly doable.