Hi S.,
We have traveled A LOT with out 4.5 year old son. We always take his car seat, though I know those days are coming to an end for us since he's getting so big now. We have the Britax Marathon which is huge! We never used it rear facing, so I can't really say how it will fit, but ours always took up the whole seat. One problem we had was that my son could kick the seat in front of him. It always stressed me out because I was always worried about him disturbing other passengers. I think she's old enough to sit forward facing on a plane because technically she doesn't even have to be in a car seat...she could be on your lap.
There are a couple of things that made traveling with our Britax seat easier.
1. If you'll be traveling a lot with your daughter, I would recommend purchasing the GoGo Babyz Travelmate. It's about $100, but TOTALLY worth it if you'll be traveling often. It is compatible with your car seat. They sell them at One Step Ahead. It's a set of wheels that attaches to your car seat so you can roll it through the airport. It's great because your child can sit in it while you stroll through the airport, eliminating the need to bring a stroller into the terminal with you. You can just check your stroller as luggage if you'll need it one you reach your destination. The wheels are FAA approved and do not need to be removed while on board the plane. When my son was little, he would sleep on flights and sometimes still be asleep after landing. We would just lift his seat (on wheels) out of the plane and roll him off and through the airport still snoozing. It was great!!
2. When installing your car seat on the plane, ask the flight attendant for a seatbelt extender. It will make the installation and removal much easier for you.
3. Check on the bulk head row. It's located right behind first class, so there's no need to worry about the person in front of you.
As for the Benadryl, there is probably no harm in it. I would just use your judgement. We always try to book flights at times when we know our son will be tired. We've never medicated him unless he had a cold or reason to be medicated. He has always slept fine on planes.
Good Luck!
A.