Should I be using my lower runes to craft up to higher ones or is the cost too much in your opinion? Am I better off just hopefully getting lucky for high runes to drop?
It’s mostly a waste of time, as you’d need tons of them to cube up to even a mid-high rune like Ist/Gul/Vex. Plus all of the gems you’d need for each combining… Ugh.
The only runes I’ll combine are Dol to keep my Hel rune supply going to keep those 35 spirit shields rolling, Io through Pul when I have an abundance of each. I’ve upgraded Gul a couple of times as well just to get Vex. The rest aren’t really worth upgrading.
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I only upgrade the low runes to save space, at some point I might stop picking them up. It would be nice if there was a special stash tab where my runes could stack, then I likely wouldn’t cube any of my runes, unless I needed one for a runeword.
I’m always upgrading and doing countess and chip runs. But I’m in a unique position where I can play in short bursts throughout the day. Dedicated time doesn’t exist until night.
Its slow going for sure, but if i hadn’t been doin it I wouldn’t have any mid runes atm at all cause they sure as hell arent dropping when I’m out hunting 
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It is not worth the time unless you need the rune that is next to it. You can upgrade mid runes when you are getting too many of them to save space, Ko to Ist. Ko runes are starting to overflow my mule and I will need to upgrade them soon. Some low runes are good to have such as Hel if you want to re-socket something but low runes are easy to farm when you need them.
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There are a few runes worth upgrading, specifically Dol → Hel because Hel is used for rerolling. Gul → Vex because the demand for Gul is very low and the demand for Vex very high.
Others you might upgrade for specific reasons, need an amn to finish a set of spirit runes, and have way to many Thul? Upgrade.
Most of the time, once you get into Um/Mal teriterritory the runes to upgrade are worth more than the rune they upgrade to. 2 Mal is worth more than 1 Ist - if you can find someone to do a trade like Mal Um for Ist.
Once you get past Vex it’s never really favorable to upgrade runes (except in the case of Sur to Ber)
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If you have like 10 of the same rune, that could be worth cubing. Outside of that I wouldn’t cube runes at all. Far more worthwhile to farm countess and trade.
There’s not enough stash to keep the low runes and chip gems. After making the lower runewords I simply had to stop picking up runes lower than Amn.
From Diablo Wiki on Zod Rune:
Counting only El Runes, it would take exactly 14,281,868,906,496 (14 trillion) through Horadric Cube transmutations to create one Zod Rune.
However, El runes alone won’t cut it. In addition, one would also need 241,864,704 Chipped Topazes, 80,621,568 Chipped Amethysts, 26,873,856 Chipped Sapphires, 8,957,952 Chipped Rubies, 2,985,984 Chipped Emeralds, 995,328 Chipped Diamonds, 331,776 Flawed Topazes, 110,592 Flawed Amethysts, 36,864 Flawed Sapphires, 12,288 Flawed Rubies, 4096 Flawed Emeralds, 2048 Flawed Diamonds, 1024 Topazes, 512 Amethysts, 256 Sapphires, 128 Rubies, 64 Emeralds, 32 Diamonds, 16 Flawless Topazes, 8 Flawless Amethysts, 4 Flawless Sapphires, 2 Flawless Rubies, and 1 Flawless Emerald.
Selling all of these items instead of using them for a Zod rune would yield 3,999,014,247,109,880 gold (almost 4 quadrillion)-enough to fill a stash to its maximum gold capacity 1,599,605,698 times.
It would take over 13 trillion el runes to make a zod.
It’s mostly a waste of time.
I keep 3 of each of the lower runes on hand in case I need them for something, otherwise I don’t really pick stuff up under sol runes.
Edit: oh, guy above me beat me there. Curse your copy pasta! 
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Assuming it takes 3 seconds to cube up 3 El runes, it’d take 150,958.364 YEARS just to get all of the Eld runes. 
Assuming each El rune takes up 8 bytes of code in your char file (I don’t know how much it takes up), 14,281,868,906,496 El runes would equal a character file totaling nearly 104 terabytes in size.