Reno to Florida. Took major highways most of the way. If you go southern route, hit Grand Canyon, Sedona, big meteor crater , Winslow AZ (just because of the Eagles).
Take old 66 through Oklahoma. Drive the Ozarks in Arkansas head southeast through Mississippi. Vicksburg and the Natchez Trace south.
When you get to the panhandle of Florida get straight to the coast (HWY 98). The purest white sand beaches you'll ever see. Drive 98 through Pensacola Beach through Destin (where I live) and follow it around the 'Big Bend' area. You can hug the Gulf Coast for along ways on you trip to the Keys.