If you had to choose only one region of Japan to explore, Kansai (関西) would be an easy choice. It's the heart of Japan; nowhere else in the country can you find so much of historical and cultural interest in such a compact area.
Osaka, the region's hub and Japan's third largest city, shows off Japanese urban life in all its mind-boggling intensity, while Kōbe retains some of the international feeling that dates back to its days as a foreign treaty port. Nara, Japan's first permanent capital, is thick with traditional sights including Japan's largest Buddha at the awe-inspiring Tōdai-ji Temple. In Mie Prefecture is Ise Grand Shrine, one of the three most important sites in Shintō, while in Wakayama-ken are great hiking and onsen, a rugged coastline and the mountaintop Buddhist temple complex of Kōya-san, one of Japan's most intensely spiritual places.
Kyoto and Osaka are the main cities of Kansai and both make good bases for exploration.