I've ridden to central Floridistan several times via non-freeway, and once to Key West. US-1 thru GA is actually a pretty good way to go for a solo-rider or two bikes, not so sure about a group. Don't know how many you have, but it can be tough keeping a group together going thru towns. It all depends how comfortable/experienced each rider is. If you keep moving and don't dink-around, you can make pretty good time. There's also no risk of a traffic jam from a freeway wreck.
Work your way south of G'Ville to McCormick, SC and pickup US221. Follow it across the Strom Thurmond dam into GA, eventually picking up US-1 at Wrens. Follow US-1 to Baxley, then south on GA-15 down to the non-existent town of Race Pond where you'll reconnect to US-1. By going this way you'll bypass Waycross, and it's even a little shorter.
Follow US-1 to I-295 around Jacksonville, picking up US-17 on the south side. 17 is a real nice road all the way to Deland, it even has a section in the northern part where you can hit "take me to jail instantly" speeds.
(a looooooooooooong straightaway with absolutely nothing out there. I was tempted, but didn't inhale)
Unless you hit Orlando in the wee hours of the morning, I'd jump over to the dreaded I-95 around it. Either way, work your way back to US-441 once around it to Belle Glade, (SE of Lake Okeechobee) heading south on US-27. 14 miles south of I-75, turn onto FL-997 which takes you to Homestead, then US-1 again. You can't get lost from there.
Not to discourage you, but from the latitude of Belle Glade/West Palm Beach, it's 230 miles to Key West. That last 100 miles from Key Largo to Key West can be a 30-35 mph crawl. Having been to KW a couple of times, I wouldn't do it again. Unless you have this burning "must ride to KW" desire, that's a long way to go on a extended weekend ride.
Have fun, be flexible.
