I wouldn't pay for business class to Florida, no matter how nice it is, because it's just TOO much money. But if the question was as the thread title, Premium Economy vs 5 star hotel, then I'd go flight EVERY time.
I understand what everyone is saying with regards to how much time you spend in the air (2 x 9 hours) versus how much time you spend in your hotel, but do you REALLY spend any time in your hotel? I don't.
I immediately rule out hours sleeping - no matter how much the hotel costs, all of them are the same with my eyes closed. As long as the bed is comfy, I'm happy. Then I'm in the parks or shopping or eating or driving around for much of the rest of the holiday - I'd say the amount of time in the hotel is probably about 2 hours a day maximum (and most of that is getting showered and changed).
Most of the difference between say a 2/3 star and a 5 star hotel are the facilities: a slightly better pool, a restaurant on site, things like tennis courts, smarter decor in the room, better quality of bathroom supplies. None of these really appeal to me - my primary wants from a hotel is that it is clean and in a good location (safe, close to attractions).
Whereas a flight upgrade is something I feel I can make use of. I'm only 6 foot tall, but I must have big knees or something as I feel cramped in economy (and DW isn't exactly small either), so more legroom and a wider seat are a recipe for starting a holiday off the right way and a chance to unwind on the way home. Extra luggage allowance on the way home is a godsend (yes, I know you can pay for that separately, but if you get it for free, that's all the better). Getting off the plane first at MCO to avoid the immigration queues is also something that appeals - that's one line I can't get a fastpass for!
So yes, if you do spend a lot of time at the hotel, then that's a worthwhile upgrade, but for me, I'll stick to flying in style...