Critters: Non-moving enemies can be covered with a custom object (CO) for a new appearance. For example see: Farik - Homeland (look in editor.) With
Purple Pineapple's KS mod you can make your own Flier, Follower (like the rat), or something that moves in a straight line. You can also toggle the deadliness of enemies. However, I like your idea better. If we could instruct the game to replace any default object's sprite sheet, that would be awesome.
Items & Power-ups: This can be simulated with a shift, a CO, a flag check, and a warp object. Put a CO representing a power-up on a shift object. When Juni touches the shift, the shift turns on the power up and moves Juni to a nearly identical screen. The new screen is missing the power-up CO. A warp object here and a flag check for the power-up in the original room ensure the custom power-up acts like the real thing. The drawback is screen flash on shifting, all objects blink out and reset. For example see: Jerom - Knytt 8bit. Again, if we could instruct the game to replace any default object's sprite sheet that would be a much more elegant solution.
Keys and Locks: This can be simulated too. You can create your own key colors using the method described for custom power-ups. Use a flag to track possession. Custom locks can be created by layering a band of color over the color stripe on a normal lock. if the background matches the band of color then it will be undetectable when the lock disappears. This also requires flag checks, warp objects, and additionally you must already have the standard key to the lock you are trying to open. For example see: egomassive - Shipwrecked. More key and lock combos wouldn't hurt, but I don't think the complexity of declaring colors would be worthwhile. Why not have 8 set colors?
Ghost Objects: I don't know about dynamically desaturating standard objects. That seems too involved. Again, If we could declare custom sprite sheets for standard objects then we could make our own intelligent ghosts. As is, ghostly CO's can be made to appear simply by doing a flag check for the Eye power-up. I know of no examples.
Music and Ambiance: Purple Pineapple's mod can loop music. Or, you can put your music in the Ambiance folder. The drawback is it behaves differently, starts and stop abruptly. For example see: Salmoneous - Mashu Prapa.
Water: I really can't get away from talking about custom sprite sheets for standard objects. You want transparent water, override a standard water object. You want non-deadly water that behaves like regular water override a waterfall object with a surface water spite sheet. These things (as well as a waterfall splash) can be done now very convincingly with CO's. For example see: Farik - Camping. (Edit: I see you already mentioned that.)
It would feel much more like being under water if Juni's movements were retarded. A new object like no-jump would be terrific for this. It could just reduce her velocity. If that's a global variable, I don't think it would be too hard to implement. If Juni's sound effects could be altered to sound more appropriate the effect would be superb. Furthermore, a new power-up diving fins could be added that would allow unlimited double-jumping when in a "retard" object, swimming! Currently, you can turn off run and high jump to simulate retardation (or weakness, see Carn - Escape from Pain), but it's not convincing.