As much as people want to dog on "Trinity," it wasn't that bad...compared to "Spider-Man 3" I think there's still enough potential that Snipes could come back in and sufficiently salvage it with a 4th.
It's not at all a situation like Batman or Superman where an outright reboot was essential following "Batman & Robin" and "Superman IV: The Quest for Peace" respectively.
I think the first "Blade" trilogy and the TV series were all made with an aesthetic and stylistic sense of integrity, in spite of the more comedic approach to "Trinity." Just tone that back down and get reacquainted with the tone and approach of Norrington's film and that's fine.
Bring in Wesley...explain the connective tissue that gets him from where he was at the end of "Trinity" to where he is now and throw Morbius at him. Solved.
If the X-Men can come back from "The Last Stand," surely Blade can do the same.