>What do you do if you create a website which modifies the dom, but find out what your users have extension XYZ which completely breaks are our assumptions about what the dom is? For example you just received a server-rendered page which should have "ul/li/span.Foo", but find out that the span is a link now instead, so your JS breaks down.

Perhaps you should move away from the "just throw some js at it" mentality and learn to design things in a more robust fashion, so that they don't depend on having to make assumptions about the dom.