2-1 has the better rewards overal (experience, coins and seeds) per point of stamina used. 5-4 and 4-3 cost a bit more stamina, and can be run less often when you start out with a full stamina bar.
What's generally ideal, is trying to get 3 medals in the highest map you can handle for which you didn't get the three medals yet, to grab the Flower Gem reward, and at the end of your session, dump the remainder of your stamina into 2-1.
Notable exception to this rule are the 11-X maps, which are RNG-hell. You wouldn't be the first not to bother with 3-medaling those and move onto 12-1 (which is a good farm spot again) as soon as possible.