There's really no simple solution, just trial and error.
Exploring is always the best bet early on. Reason is you'll find more skill books.
That makes it much easier to max out your skills. Plus you'll find everything, making more money.
As for your actual skill and perks, depends on what you want out of it. Sniper, Pyro, Energy, Melee, etc...
I never follow the story line until later, I just hit the road and start finding stuff and fighting.
Take the comprehension perk which increases your value of reading skill books, like one point.
Educated is even more like 2 or 3 extra skill points per level.
Scrounge type and Bloody Mess are a wasted level up after your first play, the novelty is gone,
now they are taking valuable points away from you that you could use elsewhere.
Intense Training, and Tag! are real valuable. I usually take the training a few times.
I stick to the risky early game exploring, it's just too fun. Go for stealth, crouching while moving, so you don't get killed.
Remember the sites with no fast travel point that you discover, so you can go back for all the loot.
Looting is very important because you need money, as it buys happiness.
Wear barter point clothes when selling if your barter skill is low. Most clothes have a certain area of value.
[i'm sure you know Rivet City discount is better than Moira's bullshit discount because she charges more.]
Remember to get the rare stuff off of the 4 Canterbury vendors early as possible as they always die.
Sometimes if you're lucky in a game, you can find all 4 bodies, getting their stash keys.
I always sell everything unless a craft item, weapon, or other useful thing, so you'll have money early on.
Just explore and find everything, and don't pass an opportunity for a random encounter.
I guess this is how I've ended up with a desk top full of skill books, and all the levels at 100.
When you're maxed out, you will miss the journey that took you there.
I always want to start a new game after the final DLC Zeta....I've found everything already.
One more note - always make friends with Casdin, and trade the Enclave stuff with him.
By game end, you'll have more than enough to keep one of each Enclave item and keep selling.
I've found more of the Enclave Outposts than the Wiki guys.