I'd have to second the 4" GP 100 .357. It may be a little tough to carry but the ammo is light and is a perfect SD round and can be used to hunt very effectively. Low maintainence and extremely reliable it would fill the bill in almost any situation short of all out war.
I had actually typed a completely different answer to this question and deleted it after coming to my senses.
A 4" Buckmark or 22/45 will do everything I need doing. Would I like to have a bigger gun? Of coarse I would and I do but if I could only have one it would be a .22lr.
This is a tough one.
I will probably go with Glock 35 for durability, capacity, price, and enhanced accuracy.
PS. I do not own any Glock product myself because I do not like them, unfortunately, having been expose to them on a frequent basis, I will admit they are a heck of a gun
It would be a S&W 3in 686. The reasoning behind this is it can be carried concealed. It can be used in any HD situation. It can used to hunt big game with high power .357 magnum loads and small game with .38 spl loads. The wide variety of bullet weights and power loads is another advantage.
Thats a tough one but for my given situation it would be a Sig P229 9mm Elite Dark with threaded barrel.
Seeing how we are not talking rifles I'm fine with only having a 9mm handgun.