Either the downtown or southside area along South Padre Island Drive are the places to stay. In the downtown area you can have a room with a view of the bay. On the southside area you will be close to restaurants, shopping, etc. I would say that both are easily accessible. Have fun.
SPID has always been most accessible to both me and my *friends*. I would suggest anything around that area as it seems most central. Hope you ladies enjoy yourselves!