It's fair to say that every MCU fan that saw Avengers: Infinity War was put through the emotional wringer from the very first sequence that saw Loki's death. From there we saw other heroes perish and the villain actually win, with the credits rolling on one of the all-time greatest downer endings ever shot. It was very much not the jolly holiday that most MCU movies had been up to that point and that's precisely why it worked so well.
So, after all of the scar tissue has started to heal, you could be forgiven for thinking that Avengers 4 would be a lot easier to take. But the stark reality is that it's probably going to get worse even as it gets better. Sure, the heroes will probably win in the end, but it will all come at a great price and it's likely we're going to see even more tragedy than Infinity War packed in.
It's not going to be an easy ride, that's for sure...
It seems particularly likely that Nebula will get her day to face off with her abusive adoptive "father" once more after her first attempt to assassinate him proved unsuccessful. The heavily augmented former villain was actually the key to defeating Thanos in the original Infinity Saga in the comics, so it would be doubly fitting for her to strike a killer blow.
More likely than her actually beating the Mad Titan herself would be her working towards freeing her sister from her presumed captivity in Soul World, where Thanos trapped her by sacrificing her for the Stone. Given that Nebula was the reason Thanos discovered that Gamora had hidden her knowledge of the Stone's location from him, she sort of owes her sister.
And it would be fitting and somewhat poetic for Nebula to realise that the Soul Stone still requires the sacrifice of one life for any "transaction" and to put herself in Gamora's position to allow her to return to her love, Peter Quill. Nebula has nothing other than the drive to kill Thanos, at this stage, and it was Gamora who liberated her from her captivity in the first place. It may well turn out that Nebula realises her debt and repays it in particularly dramatic fashion.