Since Gainesville is right on I-75, the quickest route is down I-75 to the Florida Turnpike to the Beeline East, which goes straight to the port.(Florida Turnpike and Beeline intersect each other) You will have about $5 worth of tolls. You could take SR 20 east out of Gainesville to SR100 to I-95 South. Lots of two lane road, no tolls, and some scenic countryside, but probably a half hour longer than the I-75 route. A lot depends on where your friends live in Gainesville. If they are already on the east side of town, I would do the SR 20 trip. If they are close to I-75, I would use that route. What you want to avoid is crossing Gainesville either direction whenever there is a big event at University of Florida.