There are lots of calibers that can be had in rifle configuration for lefties. They are not as readily available as the standard right hand configuration, but they can be found. I wouldn't worry so much about that as you are not going to be speed shooting zombies or anything like that.
I would focus on what your target is going to be which will determine the proper minimum caliber. For deer sized game, the calibers have already been mentioned.....243 and above. For plinking, .22 is the way to go as it's cheap and easy to shoot. For home defense, well that's a big debate, but you can never go wrong with a 12 gauge for that. Personal defense, i.e. handguns, again that's a big debate too.
So you have to first decide WHAT you're going to be mainly shooting at before you try to focus in on a caliber. There is no perfect formula otherwise. If you are concerned with the recoil of a rifle, it is usually a good rule of thumb to look at the ammunition size/weight as a gauge to the felt recoil of a weapon. For example, the FELT recoil, all other things being equal, of the heavier bullet will be more than the FELT recoil of another that is less heavy. It's physics. You can't expect a 30-06 to have the same felt recoil as a .223 because one fires a 150-180 grain bullet while the other fires an 55-62 grain bullet. Again, this is overly simplistic, but you should get the picture of what I'm trying to say here.
If not, look at the picture below and you can see what I'm trying to illustrate here. The FELT recoil from each of these calibers will be increasingly different due to the mass, i.e. bullet weight, they have to propel down the barrel. Know what I mean? BTW, from left to right, that is a .223, 30-30, .308.
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