The Donana is mostly west of the rio Guadalquivir so you may have to go north before you can cross the river. Personally, I would choose a place accessible to both, like Jerez de la frontera. You can make it to Cadiz from there in an hour and to Sanlucar de Barrameda in even less. Have some cold Manzanilla (de baril) in Sanlucar but have a designated driver: that stuff can make one very woozy!
Just west of the Donana is el Santuario de la Virgen del Rocio and further south, a Golf Resort, the name of which escapes me now.
BTW
A cousin told us that she has seen people in 4X4's driving across the riverbed at low tide. I wouldn't try it!