There is 6 different builds in Rogue: Genesia. You can only do the first one when starting Rogue: Genesia for the first time as the others needs to be unlock.

• Pure Power: This is the starting build you can do when starting the game. It will do less and less damage as you progress in Rank in the game, and you will find it to be bad for playing A-Rank but at this point you will have much more reliable and powerful build to play. It works primarily with Base Power and Power Multiplier cards.
  
• Metal Transmutation: It works with all positive defense cards, you will have a big defense and some nice damage.
  
• Zealot: This is your negative defense build. It is the most complicated build to do but it also seems to be the most popular. You will have a big negative defense, but what are defense when you do strong damage? It works with negative defense cards. Don't forget that defense multiplier become defense divisor when your defense is negative.
  
• Piercing & Shredding: This is your weird build. A build where you destroy monsters defense point by point and doing more and more damage to them. It is not exactly the most powerful build but you will find it very interesting. It works primarily with defense piercing and shredding cards.
  
• Health Transmutation: It can sometime be hard to put it in place, but it is the king. It works primarily with all positive Health cards.
  
• Corruption: You should be afraid of corruption as much as you wants to play with it.

And of course you can mix all these builds like you wants even if there is some restrictions and some mix are bad to do.

Normal challenges unlock or improve mechanics in Soul Shop. It is important to do them.
Hard challenges only give skins and/or equipments.

You can't be lock in the game if you don't do Hard challenges. But if you don't do normal challenges I am not sure you can do A or even B rank.

Advice on equipment are often asked. But here the thing, most of the game can be done without equipment.
Here is the list of challenges that need equipment to be done:

• Stoned, D-Rank Hard
  
• Cooled Steel, B-Rank Hard
  
• Blood-Handed, A-Rank Normal
  
• Soul-less champion, A-Rank Normal

It's 4 on 46 challenges.
And more than that, as saying before Hard challenge don't open new mechanics but only skin or equipment drop. You won't be block if you do them later.
Equipment is not exactly optional but is more here to help you to go toward the completion of the game than to really be mandatory. (even if in the end of course it is)

Ok. Equipment is not that important before A-Rank. What can you do with it?
Well, what do you want? Bigger AoE, bigger projectile, faster movement, defense, power, etc...?
Really, craft what you want.

BUT
In the end equipment is really important if you wants to grind the game to push it in its limits. This is the next topic.

Some challenge can be level up to offer you more difficulty. And the more you level up them the more difficult they become to the point you need equipment to do them.
And this is where you wants to craft your perfect equipment.
Sonner I listed the 6 great builds you can do. And what you need to do is to craft your equipment to empower one or more of these builds.
You will need multiple set of equipment.

Rogue: Genesia is modable in a lots of way.
Feel free to mod it and to do mods to your liking.