Depends. Generally mom would want to be in the back with the newborn unless it's a very short flight. That argues for putting the three yr old in the right seat. However if he/she is inclined to kick the yoke (assuming in a car seat) or play with yoke, mixture, etc (assuming not) then both kids should be in the back. On the other hand if three year old is jealous and wants to suffocate newborn, front is better.
Can the wife be a pinch hitter and/or function as good right seat help? If so right seat for her. Even better if three year old can do basic newborn fixes such as replace a fallen pacifier into mouth. I am assuming newborn is facing rear, I don't think the carseat is legal otherwise. You probably have the mirror thing set up in your wife's car but if not in the plane your wife will feel uncomfortable not seeing the baby's face if she is up front.
What it really boils down to is this: if the newborn doesn't sleep the whole flight (odds are he will but you never know) can your wife stand the screaming if she is up front and can't remove him/her from the seat to nurse? If bottle fed maybe three year old can hold a bottle but there's the whole burp and spit up thing - bottle feeding in a car seat not ideal. Breast feeding in a car seat even less, don't ask me how I know.
There's one more thing I almost forgot, newborn necks are weak and in rear facing position the head may flop forward during acceleration and climb out. Can three year old be relied upon to gently keep his head in place? Oh, and this would be with newborn's hearing protection headset in place?
In retrospect if I had it to do all over again I would let dad and three year old have special airplane "lessons" while I stay home with newborn.
Hope this helps!