You would lose detail by shrinking your sprites, not to mention it'll probably look awkward.
No, you wouldn't lose detail. Why would it look awkward?
Zooming et al in Construct is done before applying texture maps (sprite images) so it would look just the same.
You would only lose precision, so in a large layout you could run into rounding issues. I believe it's a bad idea but not because of sprite distortion but because simulating your whole world at once could get slow, depending on how your game works. Also... come to think of it... a large zoomed layout would be just the same as a larger layout but with rounding issues... so it's just not helping.
if you NEED to simulate warped NPCs in detail (colliding with walls, etc) then do big layout. If it's not really important (very likely, most games do this) then just store the NPC data somewhere you can retrieve it when you go to that layout.