The following contains significant spoilers for Avengers: Infinity War.
Avengers: Infinity War will certainly have some significant implications for the future of the Marvel Cinematic Universe, but possibly none more so than the already announced Guardians of the Galaxy Vol. 3. The new movie ends with the outer space team in a pretty bad way, and even if, as we expect, most of the damage will be undone by the end of Avengers 4, it seems likely that there will still be long-term consequences of this film that will have to be dealt with in the planned third Guardians movie.
We know so little about what Marvel is thinking in terms of Phase Four of the MCU, but the two movies we do know for sure are coming are the sequel to Spider-Man: Homecoming and Guardians of the Galaxy Vol. 3. We also know that the third Guardians movie will be the end of the road for the current iteration of the Guardians team. Of course, based on what happened in Infinity War, there's a good chance we may have already seen that end.
At the conclusion of the new film, only one member of the Guardians is left standing. Rocket has survived while Groot, Drax, Mantis and Star-Lord have all fallen victim to the Infinity Stones. In addition to that, Gamora was killed by Thanos as a sacrifice in order to obtain the Soul Stone. At this point, the expectation is certainly that the use of the Infinity Gauntlet will somehow be reversed, bringing back to life all, or at least many, of those that were taken by it. If that happens, it may bring the rest of the Guardians back, but it will still leave Gamora dead. (Or not. Anything's on the table at this point.)
When James Gunn first announced that he would return to direct the third installment of the Guardians of the Galaxy, he said, "It will conclude the story of this iteration of the Guardians of the Galaxy" which, while that doesn't necessarily mean the characters will all leave the MCU, implies that the team will be changing by the end of this new film, or at least before the next one, if and when there was one. However, it seems quite likely that this iteration of the Guardians may already be over, which could be exactly what the next film will be about.
While Avengers 4 could certainly bring the entire Guardians team back from the dead, Gamora included, doing so would cheapen everything that Infinity War did, and as such, it seems likely that Gamora at least will stay gone. With so many characters and storylines to juggle, it seems unlikely the next Avengers will movie will be able to adequately deal with the fallout of this for the team, which means Guardians of the Galaxy Vol. 3 could very well be about how the rest of the squad deals with a missing teammate.
Guardians of the Galaxy Vol. 2 was a quite emotional story, dealing with the relationships between children and their parents and the importance of family. In the case of our heroes, this tends to mean the family that they have made together, rather than the ones they were born into. Every member of the Guardians has had a tragic life that they begin to heal from only after finding each other. It makes a lot of sense then that the last step of that healing process may actually be dealing with the loss of a member of that family.
Peter Quill's relationship with Yondu (Michael Rooker) was a difficult one and while the end of Guardians Vol. 2 saw Quill saying goodbye to a father figure, it was more about coming to terms with his past. Peter never saw Yondu as a father at the time. His relationship with Gamora is onething else. Avengers: Infinity War shows the two together romantically for the first time and while it's unclear how long their relationship has been like this, there have been years that have passed between the events of Guardians Vol. 2 and Infinity War from a story standpoint, Peter and Gamora certainly see each other as family even if it's only been recently they've become more than that.
What's more, Gamora has always been, as unlikely as it sounds considering she's a former professional assassin, the moral center of the team. She's the one at the beginning of Infinity War who says they need to answer the distress call for no other reason beyond the fact that people might need help. How will the rest of the Guardians react without that voice?
Whoever the villain of Guardians of the Galaxy Vol. 3 is will very likely be inconsequential to the story the movie may really try to tell, one of a family grieving.
Without knowing where Avengers 4 will take the story of the Guardians of the Galaxy, it's impossible to know for sure where the team will be at the beginning of Guardians of the Galaxy Vol. 3 (or even WHEN on the MCU timeline that story will take place). However, it does seem very likely that the story we get won't simply be other fun, outer space adventure with the same characters so many have grown to love.