Keefe should be gone - that's 5 playoff series with 4 losses, and the only series win we had included large stretches of very poor play by us and repeated failures to show up at the start of games with anything resembling quality effort (ie we were actually pretty lucky to get some of those TB wins).
Beyond that, I think one of Matthews/Marner needs to go. They'd need the biggest trade return, clear the most salary, and are the two core guys whose playoff play is consistently below their regular season play (well Tavares too, but I don't think we can move him). Moving one of them would also simply provide the benefit of shaking up the core/locker room, and their trade value is high enough to bring back high quality pieces to fill specific needs (eg youngish physical top 2-3 dman).
Hard to say which one though given the NMC status. Both of them have NMC kicking in July 1st. If we trade Marner, is Matthews willing to re-sign here? If we trade Matthews, we at least have another year before we'd have to re-sign Marner, though him having the NMC hurts us if he decides he wants to leave. Trade both? Ideally we wouldn't, because as much as they've struggled in the playoffs, they're still 2 of the top 5 forwards in franchise history, and I think you'd need to hope that with a revamped core, the one that stays could perform better in the playoffs.