Personally in my opinion it has to be rear wheel drive. I've driven a number of cars with FWD on a few trips and I wasn't that thrilled.
I love my Volvo 960 with it's 2.9 liter 24V, I6, motor that gets me 28.2 mpg at 65 mph. As far as seats go, there isn't much offered out there better than a Volvo seat for long distance driving.
There are a few cars that I think would be great highway cars but not much that is new. The 94-96 Impala's as well as the last generation of Crown Vics would fit the bill. A larger Mercedes like an E or S class sedan, or a Lexas LS would also make great highway cars. BMW, I'd go with a 540i with the 3.0 liter motor, the 3 series is too small. You want a 6 cylinder or 8 cylinder for the highway because the fours can be a little noisy at higher speeds.
Here's the thing about road trip cars especially if you plan on driving distance and spending more that a couple days on the road, you need space for your luggage and trip supplies. That means a trunk is a necessity. I've owned wagons and cars with hatches and I would always wish I had a trunk when I took them on a trip.
The one thing you need to think about is a balance between size, comfort and fuel economy. With the cost of fuel today any vehicle choosen for long highway trips has to get in the high twenties, low thirties with gas mileage.
I did rent a 2020 Impala for a trip close to 2500 miles back in March when my Volvo decided to puke power steering fluid from almost every seal. Considering it was a GM I have to admit it was a nice car for the highway. The 305hp V6 was more than adequate for my needs but again I'm not a real fan of FWD for long highway drives. It did get 35-36 mpg at 65 mph and I wasn't running anywhere close to those speeds, more like 75-80 mph and I got 30-31 mpg. If I needed to rent another car for a long trip my first choice would be another V6 Impala.