Whereabouts in Kissimee are you going ?
From Sanford I've always found the easiest way is I4, come out of the airport turn right onto Lake Mary Boulevard, ignore any signs for I4 turning off and keep going straight until you actually hit I4 at Junction 98. Head west towards tampa and exit at 65 or 64 depending on where in kissimee. I4 is usually busy but moving, tends to snarl up after the kissimee junctions.
The other route is to use the 417 greeneway but as stated this is a toll road and sanford to kissimee will cost around $6.50. Last thing you need is fumbling around for money at toll booths after an 8.5 hr flight. However, all the holiday and hire care operator tell you to go this way.