Using the InputManager system to modify other applications definitely counts as an awful hack in my book. The intent of the InputManager API is completely different, it's only a convenient (and fragile) side effect that allows it to be used this way.
APE is somewhat better, but it's still very very easy for haxies to make assumptions about the internals of a program that change between versions. Anyone relying on scrollable areas of web pages being WebDynamicScrollViews would be broken by Safari 4, for example (older versions of Adium did this).
As an additional note, all the WebKit/Safari team members I've spoken to about the matter have mentioned that Safari modifications that rely on private details of the implementation are a serious problem for them, and one of the most common causes of crashes. Typically that's things like Saft or PithHelmet, not ad blockers, but something like ClickToFlash or GlimmerBlocker really is less fragile.