An in-flight assassination sounds like it would be a vignette more than a proper level; how big can a plane get? How many interesting branches would it have?
And how would you escape the level? Parachute from a passenger jet? Click on your assigned seat and blend in as a regular passenger - particularly effective if you got rid of the body so that it isn't found until you land? Maybe, rather, you could have the level start on the airport and you could choose to ambush your target before the flight.
Some of the Hitman: Contracts levels, in particular, did that - a roaming target would be enjoying leisure at some location, and change it from time to time, be it a toilet break, a sauna, or casino. The dentist in Traditions of the Trade, Fritz Fuchs, was like that - the problem was that he didn't rotate between locations particularly often. A savvy player who already knew the level, in order to perform a more interesting assassination than the tried-and-true thermal bath/sauna ambush, would have to pad his time and wait for more than 10 minutes just for the target to consider moving from his place. Hitman levels aren't, generally, as sprawling as Thief levels; 10 minutes for a level is a very generous time for a single clear, even if you go into a mission blind. There was also Deadly Cargo, a level which is broken up into a few timeline segments, and you can even speed up triggering them if you know how to, though it's not particularly obvious - the target meets up with a man who trades him a nuke (if you kill the man, the timeline skips ahead), then the SWAT team who caught whiff of the trade assaults the ship (if you assume a SWAT member disguise, you speed up the timeline), the target threatens to detonate the nuke (if he dies while the bomb is armed, he detonates the bomb in his death throes), a helicopter shows up for his extraction (you can take it instead, and you can even usurp him and walk plain in the face of the SWAT members with your detonator).
Maybe if you could start off at an airport and have a bit of a timeline where you have an early window of opportunity to kill the target before he boards a flight, an opportunity to join him in-flight, timing your kill to be unseen before you leave the flight at the next stop, or maybe straight up dumping the body off of a plane.
About the only unfortunate implication I could see is players choosing to mine a plane and then blow it up, kiling everyone onboard - sounds a little sensitive. Given how ICA tends to run cleanup crews, Diana would probably be fairly scornful in the post-mortem commentary. Also, 47 is, generally, not a terrorist; I think I even saw a statement a while ago that said so. So, in order to prevent that from being an avenue (which, frankly, isn't particularly interesting, either), you could have this be some sort of an Air Force One movie situation; the ICA catches whiff of some renegade operation by a rival organization (Lord knows we've had like three of those in the lore already) and installs their agent to snuff out the candle because important people are on the plane. You maneuver the plane, either installed in as a terrorist or, alternately, in a "hostage" or "pilot" outfit (47 *can* pilot a plane) and quietly remove everyone while rescuing not-Harrison Ford. And if you get found out, important hostages will be put in danger, kinda like A Murder of Crows.
(I wrote a wall of text being skeptical of this one particular idea, and then it got me thinking. Fun exercise.)