A custom saddle made to fit your weight and riding style is a huge improvement over stock. Every bike I own will have that figured into the purchase price.
There are simpler/cheaper options (gel pads, air cushions, the local upholstery shop) that vary in price and quality which may work for you or may not, but you won't know until you've already spent the money.
But one other important and often overlooked thing to consider for real long-distance comfort is what goes between you and the seat.
Jeans or work pants are good for everyday wear, but just don't cut it for long rides. Besides having seams that you sit on which cause irritation, they can retain moisture (either sweat or rain) which is bad for your skin. And they offer no padding or abrasion resistance, so even a very low-speed slide will result in some serious damage to your legs.
Some guys try creams, powders, and even padded bicycle shorts, none of which provide any real comfort, and all of which add other problems, such as clumping, sweating, and seam irritation.
Personally, I like the Aerostitch AD1 Pants
, which are waterproof, breathable, comfortable, and have no seams to sit on. Under that goes LDComfort Undergarments
, which are also breathable, comfortable, devoid of seams to sit on, and actively wick moisture away from your skin to avoid sweating, rashes, and irritation. I've tried many other brands of under- and over-pants in the past, and none of them have worked as well as my Aerostitch and LDComfort gear.
I have ridden more than a hundred different thousand-mile days in that gear, and dozens of 1,500-1,600-mile days in complete comfort in all weather conditions. Can't ask for much more than that.