They’re going to have to throw some nostalgia baiting in there somehow. I stopped believing MLP writers saying ‘these things aren’t going to be in here’ long ago so I don’t see why the G4 main cast won’t have some part here, even if indirectly. If they’re boxing themselves in like this setting it in the G4 universe out of an admitted attempt at baiting old fans, they’re not just going to go for a clean break.
My guess is Twi and pals left sometbing the new main cast will find on their journey and use to save the world. Either a deus ex the main cast will use to unite the world (like some holocrystal with twilight giving a speech on friendship broadcasted on tv for example) or something like a book, letter, or some type of object from the old cast that shows how important friendship and harmony are that inspire the new cast to complete their journey.
Either way, I call bs on the g4 cast not playing a part somehow.