OH man... I hate to say it, but there is NO good answer here that will work for everyone. Holster comfort depends largely on body type. Size of your midsection often determines which kind of holster will work for you. IWB is not comfortable for fellas with larger midsections. High ride is not good for guys with shorter torsos. Way too many variables here and one size never fits all. But here are my personal observations of many years of carry.
I've carried since it became legal in 1995 and I'm always searching for the perfect holster. It's kinda like the knife bug TBH. The highest quality holsters I own and use are Milt Sparks and Mitch Rosen. Other custom makers also do a fine job.
As far as different ways to carry, there are many. Ankle is very, very very concealable under long pants but not very good while upright since you must kneel to draw. While driving ankle carry is excellent, far better than any waistband carry since the seatbelt generally restricts drawing. Pocket carry is also very concealable, but worthless while sitting. Sitting makes your gun unreachable.
IWB is very good for concealibility. It is also pretty comfortable with a good holster. The Sparks VM2 is very hard to beat for comfort, and quality. It's not cheap, but how many quality items are cheap. The problem with IWB is you must make a wardrobe change. Add 2 inches to your waist size and buy a good solid belt adding the extra inches too.
Shoulder holsters are only worn in hollywood movies and by people who wear white pants and pastel shirts. It's not comfortable and not very concealable or practical to run around in a buttoned jacket. It's also a very slow cross-draw action. Bad idea.
OWB is fine so long as you have a very minimalistic design that doesn't 'print' through your shirt. Longer shirttails may be required depending on slide or bbl length of your gun. OWB requires no wardrobe changes generally.
So, the answer is... there is no answer that works for everyone!

Just remember you will be sitting, driving and standing throughout your day. A lot of fellas carry two for this very reason. An ankle carried backup can be very reassuring. 3 o'clock IWB or OWB with a 45ACP and a nice little J Frame on the ankle covers your bases pretty well.
EDIT TO ADD: If you don't have a good solid belt, no holster in the world will be comfortable. I like the wilderness products. The Frequent Flyer belt is very lightweight, very durable and works very well.
.