What Do We Know?
Let's leave rumors and speculation aside for a moment and let's think about what we actually know about the games
1) There will be two games; one will be "Ground Zeroes" and the other one being "The Phantom Pain."
2) Ground Zeroes will be the prologue for The Phantom Pain, and while the gap between those games will be of 9 years, we don't know how long has been after the Peace Walker incident.
3) At this point, Snake and Liquid were born already.
4) Paz's mission was successful in spreading the word about the actions of MSF, so a UN inspection was coming to Mother Base.
5) Chico apparently will betray MSF
That's all the confirmed information that we have about the game, at least until now. There isn't a lot of material that would allow us to know exactly what's going to happen in the game, however we know enough to speculate and perhaps, actually discover one or two important things.
First, let's talk about the games themselves. During the presentation at GDC, Kojima said that Ground Zeroes and The Phantom Pain "when put together are Metal Gear Solid V," which makes you think that Ground Zeroes will be this game's version of the Virtous Mission in Snake Eater, and The Phantom Pain would be the real deal. However, Konami released a statement saying that they are two different games. It does make sense, actually. If Kojima wants to show the downfall of MSF and Big Boss, I think it would require a lot more than just a couple of levels as a flashback in Metal Gear Solid V.
Now, let's go to something else that has major relevance to the story. How long has it been since Peace Walker? Just by looking at Chico and Snake you can guess that it's been a while after the incident, since Kaz actually says to Big Boss "Age hasn't slowed you down one bit," and Snake didn't look too old in Peace Walker if you ask me. If we take in count that Paz was found by someone after the final battle in Peace Walker, and that she was held for interrogation at a prison camp, we can speculate that at least one or two months have passed after the game. And this brings me to another important aspect of the game, Who are XOF?
We know that Paz worked for Cipher, and it wouldn't make sense that they would torture one of their own for information, so it's very likely that said group isn't related to The Patriots. And judging by both trailers it's very likely than they will be the responsible for the destruction of Mother Base, apparently with the help of Chico. What did he say to them? What will he do during the destruction of Mother Base? What was he doing at the Prison Camp? We know from Kaz that he was in contact with Mother Base before he was captured, he was there on a first intent to rescue Paz? Or he was just doing some research on the place?
Speaking of trailers, thanks to the latest trailer we now know that Ground Zeroes won't have a happy ending: Mother Base will be destroyed, Big Boss will be in a coma, at least half of MSF will be dead by the end of the game. And once all that stuff happens, what will be left after 9 years? Let's speculate for a moment and say that the reason why the soldiers killed every single man in the hospital scenes of the trailer was because they're wiping out what's left of MSF, with the hopes of killing Big Boss in the process (this reinforces the theory that XOF isn't related to Cipher, since they're interested on Big Boss joining them), and during the first portion of the game you'll find out what happened on those 9 years, who survived, what was lost, and most importantly, why "the world want's dead."
According to Portable OPS, after Major Zero founded the Patriots (along with Sigint, EVA, Ocelot, Big Boss and Para-Medic) some members left the organization because of conflicts with its leader, among those people you find Revolver Ocelot. And if you've seen the trailer you'll notice somebody very familiar helping Big Boss while he was escaping of the hospital.
Again, the same questions come to my head: What is he doing here? Where was he all those years? Why we didn't heared of him during the Peace Walker incident? Why he came to help until this point? Was he involved during the fall of MSF? This is the kind of things you have to love about Hideo Kojima, he knows what the audience likes, and knows when is the right moment to put a character back in the plot. The only question that remains is "why now?"
Another thing that a lot of people have noticed in the trailers it's the presence of a very creepy child who will torment Big Boss during his escape of the hospital. Psycho Mantis is definitely a fan favorite, and a lot of people would be very happy to see this character back in the story. While I can't say that I wouldn't be happy if the creepy kid was Psycho Mantis, I'm not really sure how he would fit into the plot, we really don't know that much about Psycho Mantis anyway, so who knows? Maybe it's another character which has the same abilities.
And finally, another thing that has been through my mind lately is the presence of a character only known as Ishmael, voiced by Kiefer Sutherland. We don't know that much about him, only that he has been looking over Big Boss during the 9 years he was in a coma. Obviously he must be a member of MSF, but which one? Was he left by Kaz to keep an eye on Big Boss? Or he was just another soldier who admired him? Is he Gray Fox, like some fans have been speculating?
I personally think that he is the guy that Kaz mentions during the trailer (at the beginning, when he says "What about him"), and that he'll play a major role in the game. He might even become a member of Fox Hound in the future.