how would you GM something like a "shapeshifters impersonating the PCs" situation?

[Varyon]

A lot will depend on what the shapeshifter is doing - if they're only doing nefarious things "off screen," you could actually leave the player who is controlling the replaced character completely in the dark, particularly if the shapeshifter is a perfect impersonator. If the shapeshifter needs to do nefarious stuff "on screen," concealing it as though it were normal behavior, that's generally going to require the player to be in the know.

Of course, a lot also depends on your players. For some players, they can sufficiently divorce player-knowledge and character-knowledge such that you could literally game out Alex Mercer murdering, absorbing, and shapeshifting into the unfortunate PC in front of all the players, and when he shows back up amongst the party, they'll have their characters behave as though it's still their friend. Others? Not so much.

If I wanted to do a "shapeshifter replaces one of the PC's" plot (and honestly, I don't think I'd want to), I'd probably let the players know ahead of time that that's a thing that may happen, then probably at the end of the first session (of that story arc) I'd have the PC's split up. After that, I'd arrange one-on-one sessions with each player to game out what they do when they're separated - and for at least one of them, part of that would be an encounter that could result in the character's death or capture, in a manner that would allow the shapeshifter to take their place. If any fail, those would be the ones I could have play as the shapeshifter in the next session (possibly the next several sessions, depending on how long the plot goes). If they all succeed, then if the shapeshifter didn't get captured/killed during one of the solo sessions, I'd have it take the place of an NPC (probably with more hints than they'd get with it taking the place of a PC, as a reward for nobody getting killed/captured).