I-81 isn't bad...but for the winter, keep in mind it goes thru the mountains (snow?) and then ends at I-40. I've only taken this route during summer...and it is nice.
I-95 is the most direct from beautiful downtown NJ, I've done this trip quite a few times. I always take the bypasses (Baltimore, DC beltway and Richmond...without a map, I think the route numbers are Balitimore:695,DC Beltway:495 westbound and Richmond: 295
I leave my house around 4AM just to get past the DC beltway before rush hour...even if I leave on, say a Saturday. Baltimore and Beltway add maybe 1/2 hour each to the trip...but much better roads and traffic....I surely don't want to drive my motorhome/toad thru these cities at ANY time.
My usual schedule of travel/overnite stops is: first nite, Florence, SC RV park, used to be a KOA. 2-3 gas stations at the exit, both easyin/easyout. Campground on the other side of I-95. Second nite, Ga exit #1..KOA. St.(Jacksonville north KOA?) right on the Ga/Fl border. Nice place. 3 gas stations, all easyin/eaasyout. From there...Florida is a long long state. Many gas stations and campgrounds along the way. Check out, for instance, the Trailer Life Directory and the KOA directory.
My OPINION, regarding Key West, make sure you have a RESERVATION where you intend to stop....there is only one way in and one way out...you want to make sure you have somewhere to stay. Simply parking somewhere overnight is a no-no...the last time I was there.
g'luck and enjoy