
Definitely come to SoWal for a girls trip. You'll want to decide whether you want to stay East end (Rosemary Beach/Seacrest area - closer to Panama City Beach so you'd fly into Panama City airport), middle (Seaside/Watercolor/Grayton), or West side (other people know more about this than I do but you'd fly into Fort Walton Beach airport, which is sometimes cheapter than Panama City airport). I'd recommend something within walking distance of some nice things -- e.g, coffee shops, shops, restaurants, whatever. Seaside would have all of that in one place, but it will be busiest that time of year so it depends whether you like that or not. Rosemary Beach and Watercolor also have restaurants, etc., within walking distance, all in their community with Rosemary Beach having more.
Then there are many smaller communities near and far from these communities which may be within walking distance or just a few miles from plenty of places to go. The farther away you are from the bigger communities and public beach accesses, the quieter the beach will be.
Go to VRBO and check out the different communities - just type in "Rosemary Beach", Seacrest, Seagrove (also a nice community with lots going on within walking distance), Seaside, Watercolor, Grayton, Gulf Place (and others can tell you more about the west end of 30A), Sandestin. Though not right on 30A, I've heard Sandestin is really nice and spa-like.
I'd rent a home/condo with 3 nice bedrooms rather than have separate rooms.
For a girls-get-away I would:
Go to a spa for a day and definitely get massages, manicure, pedicure
Eat out at nice places
Shop
Try to do healthy things like walk, bike, etc. - find out about yoga on the beach
Go to the free outdoor movies/concerts at Seaside, Rosemary Beach, and Gulf Place (probably Sandestin, too)
Hang out in breakfast places in the morning - I love Fonville Press at Alys Beach (east end) and people are saying great things about Flip Flops in Seagrove.
Watch an awesome sunset every evening
Sit on your porch/deck (get a place with a porch/deck) and have breakfast, read, take-out meals, etc.
If you come to 30A, I'd plan to stay on 30A (SoWal) because the Destin traffic can be nasty during peak times, as can the Panama City traffic (though I think Destin traffic is worse)
Another trade-off would be money. the more you spend on the place, the less you have to spend on some of the extras (spa things, restaurants, etc.). On the other hand, if you love the place, you may not want to leave it much.
Enjoy your girls get-away.