There are many other islands in southern Japan that seem large enough for B29 runways (the current runway is 2 miles). Why didn't the USA pick the island of least resistance? I'd assume Okinawa was the most fortified due to its size and local population.
The Allies weren't taking Okinawa for B-29 runways. They had those already in the Mariana Islands. A B-29 airfield was built on Okinawa, but the first attack from it against Japan happened on the last night of the war.
The primary reason for taking Okinawa was as a base for the invasion of Japan, both for ships and shorter-ranged aircraft. Okinawa has harbours, and Kadena Air Base had already been built by the Japanese.
This required taking all of the Ryukyu Islands, and that's what was done. The Battle of Okinawa is the famous part of this campaign, because the Japanese concentrated their resistance there, knowing that while they held the main island, the other islands would be of limited use. You can't set up mobile fleet bases while the enemy are still within artillery or small-boat attack range. The other islands in the group were taken comparatively easily, so the combats are not famous.
Sources: Okinawa, 1945: Final Assault on the Empire, Simon Foster, 1996 and Okinawa: The Last Battle, the relevant volume of the US official history, available here.
Addendum: Of course, once you have a base, other uses for it emerge. In July 1945, Halsey's Third Fleet attacked the Tokyo area, and then, as best the Japanese could tell from radio intercepts and direction-finding, moved south. This was confirmed when carrier aircraft attacked Kyushu, the southernmost main island of Japan, and Japanese aircraft were moved south for a counter-strike on the Third Fleet. But it wasn't there. The radio intercepts had been staged from the USS Tucson, which had separated from the fleet, carrying radio operators from Halsey's staff and sailed south, imitating Third Fleet's traffic. The carrier aircraft had flown from Okinawa.
Third Fleet was located again when it attacked steel plants and rail ferries in Hokkaido and northern Honshu, and the Japanese were unable to retaliate effectively. This raid sank eight and damaged four of the twelve rail ferries that carried coal from Hokkaido to Honshu, cutting the amount of coal that could be transported from the mines in Hokkaido to industry in Honshu by 80%, and crippling Japanese war production. Source: Holt, The Deceivers, pp. 769-770.
Okinawa is the largest (by far) of the Ryukyu Islands. Given the importance of these islands, as discussed in the rest of the answer, this made Okinawa the one to own. That is, Okinawa had room for "runways," harbors, and other facilities, in addition to its strategic importance.
A large part of the importance of the Ryuku Islands stems from the fact that it is a chain of islands that more or less link Japan to Taiwan, and points south and west. With the possession of those islands, America could completely cut off the Japanese Home Islands from its possessions in China. Had the atomic bomb not been dropped, the year 1946 might have featured an invasion of Japan simultaneously with the liberation of Japanese held China.
From an "invasion" perspective, the Ryukyus generally, and Okinawa particularly, were close enough to the main Japanese islands for both ships and short-ranged aircraft to be a menace to Japan, and yet not so close as to meet the "main force" of the Japanese defense. This made them an ideal target for a "preparatory" invasion in 1945.