Yes, it matters.
The first decision you have to make is the general location where you want to stay, as the island is 25 miles long (though as a practical matter the hotels are not that spread out). The main general areas are North Ambergris (above the river channel), in or at the edge of town, or south of town.
Then you have to decide on price level. Prices start at around US$15 for a non-A/C room and go to over US$300 (and much more than that if you stay at Cayo Espanto on a little island on the back side of Ambergris).