There are a few ways to go about this, depending on the scope of whatever you are trying to achieve.
A straightforward way would be to build your game engine around external files or project files loaded by AJAX. They would contain the values for moddable variables in your game. If you change the project file, then different values would get loaded.
From there, a more advanced option would be to load sprite assets from URL, again either from project files or external files. You can have an xml document to provide a list of links to all assets that need to be loaded, and change that file if you want different assets.