Preface: I love the in medias res technique in literature and I am fascinated by its potential uses in gaming. I even named one of my campaigns In Medias Res because that's how it started. Despite that, I am skeptical that it is a general purpose, out-of-the-box tool for everyday use. There are both player management issues and narrative design issues that I will address in turn... mostly separately, because they do intertwine.
Player Management: In brief, I would never spring an in medias res type setting on players without at least informing them before hand, and ideally getting an affirmative buy-in from them. There are some players who will be very uncomfortable with the entire idea, and in my experience they are correlated strongly with players who enjoy designing histories and preexisting relationships and plot hooks for their characters before they even begin playing. It is difficult—not impossible, but difficult—for a player with strong preferences in that direction to tolerate or think/role-play their way around a glaring disconnect between their built-up history on the one hand, and the present game situation on the other hand. On the other hand, there are some players who will positively adore it—in my experience, this correlates well with players who do not like to come up with detailed pasts, either because they are too busy in real life, or because they draw more meaning from played events than from past events.
This is not a value judgment. This is simply an observation that players crave in different measure exactly the information that is removed from by this technique. Some crave it not at all, some need it like they need oxygen. This is also not absolute, it is merely a trend that I have noticed.
I will also note that it's hard to tell unless you have direct gaming experience with someone; simply knowing their literary preferences is not really enough. I am an example of that: As I said, I adore the literary technique and gobble it up. I also prefer to design histories for my characters, and I doubt that I would put up with any of my own experiments unless I really trusted the GM.
So I would absolutely brief the players and... effectively ask permission, as the first step.
As the second step, I would start asking what sort of constraints they would be comfortable with, and what sort of guarantees they would require in order to make this viable. In your example, I might expect something like, "You're not going to make us the bad guys, are you?" Or, "You're not going to screw us over and have us targeting or accidentally killing the wrong people?" Or perhaps, "We need to know that our characters will have access to decent information, and we don't want this to be a prelude to just getting mobbed and captured." This is going to be highly situational. And I would be asking things like, "How much scripting will you put up with, and for how long?"
One real-life gaming example split the ticket: One of the players was effectively starting in medias res literally in the middle of an action scene (chased through a forest) with complete and total amnesia. But I handled this by advertising to the group that there was a great narrative role for such a character and if anyone wanted to volunteer for it, great—otherwise, I'd make it an NPC or just restructure so the character wasn't necessary. A player who had less time than the others to do detailed character work took me on it and laid down some conditions like, "I am not the bad guy," and "No icky romances with unknown family members," (this made sense in background) and similar. I agreed publicly in front of the other players, requested maybe half a game-session of light scripting/pressure on that character—enough to get in contact with the rest of the PCs—and we were good to go. (The other PCs had no memory issues and did not start in medias res.)
Had I tried to shoehorn other players into that role, it would have gone worse. Terribly badly in a few cases.
Narrative Concerns: Even with partial (as above) or full player buy-in, there are still concerns about how to structure the game as a whole. RPGs are not linear literature like movies, books, or plays. And another respondent points out that in the middle of things does not mean without information. I would put a finer point on that and say that RPGs are not linear media precisely because the players are not spectators, the players have agency, and using the in medias res technique creates a direct and very strong tension between the characters who are merely in the middle of things but are not without information, and the players who are both.
I will pause to point out that this is exactly what you say you want-- you want them not to [need to] know things like what city they are in, who they are fighting, what the MacGuffin is, etc. But consider, beyond notions of player buy-in, beyond notions of the players thinking this is unfair, of how exactly the players are to exercise the agency on behalf of their characters that makes this a game without having access to the knowledge of the characters?
This is a thorny problem, but there are some techniques that can work to some degree. One is the full-party or single-character amnesia that I used as an example, and another respondent suggested. Here, the problem is solved directly: There is no knowledge that the players have access to. They are all agency and no history.
But a subtler technique is to (again, with an appropriate degree of buy-in) let the players establish their character histories and then play the event of, or the immediate aftermath of, the game world forcing a radical change in circumstances.
One example from play is from a Nobilis game, where the characters are sub-demigods with mortal pasts, existing in a mythic headquarters. The game typically assumes this ascension to demigodhood took place in the past and that the characters are established in their role. I decided to play from the moment of that ascension forward—there was suddenly a host of new information to assimilate, new characters to understand, great events happening in the game world into which the characters were swept up without knowledge, etc. It was not "bullets whizzing past your head," abrupt, but it was close enough to call the game In Medias Res. Even for that, I got permission from the players.
This structure can be replicated across genres and in greater or lesser degree:
- A group of modern day citizens are exposed to a super science experiment gone wrong—this is a superhero genre game where the characters are very suddenly super-powered mutants.
- A group of frontier scouts comes back from patrol to find a smoking hole where their border fort used to be, and they don't even know where the frontier is now.
- A group of soldiers at a border outpost has to repel an attack from a stealthy, unknown enemy.
Notice, by the way, that all of these scenarios are in some way reactive as opposed to the pro-active situation you describe. The questions all naturally focus outward—not, "Why are we doing this, where are we?" but "Who are these enemies, what just happened?"
And notice that to a degree, you can either play through the entire event, or you can open a little later with, "You've been fighting off an attack on your base for half an hour, here's the state of the battle."