My 2 cents.
1. The luxury lines have more original itineraries, especially in Africa and India. If you want to venture to some destinations, you can't go on a mainstream ship.
2. The food at the specialty restaurants aboard NCL / Celebrity, were just as good as the luxury lines to us. One luxury ships we were on had a Michelin rated restaurant, but noone seemed to use it.
3. The food can be heavy at the main dining room on both types of ships. Luxury lines load up on butter and cream. Main stream lines load up on oil.
4. Very few kids on luxury lines
5. We've met interesting people on all of our cruises, but hands down the biggest characters (in a good way) have been on luxury lines.
6. Depending on your style of entertainment, you'll have a clear preference. Luxury lines will have a talented concert pianist and main stream will have a broadway style show.
We used to cruise for the 'cruise experience'. For that I'd say the luxury lines win hands down. Now we cruise to spend time together as a family. For that the mainstream lines suit us better.