I'm confused how some of yous say you won't want Konami to return to the old canon because "there's nothing left to explain/show, we already know what happens etc." but a prequel to LoS would be just as much redundant, because likewise we already know what happened to the Brotherhood, how things came to be, etc. so yeah. At that point it just boils down to, do you prefer coke or pepsi.
The best bet I think would be for them to make a canon that mirrors the classic timeline/story but doesn't strictly adhere to it. Ya know the same basic idea that was introduced in CVIII and onwards, Trevor being the first to kill Dracula, etc. but include a new take on things, different plots, gameplay, etc. That way it'll still feel familiar, yet new at the same time.