My favorite combo: Over 9000 blocks per minute and half a trllion picks (Yogg's Plasma Snowball TNT) +analysis +looking for improvements, advice, and approval before I turn this into a guide

[3ICE]

Abilities: Snowball to one shot creeps, TNT for extra clicks.
Use all of your enderpearls to transcend player tree
Get Block Fortune +10
Equip four high level Fortune-boosting items
Kill boss for +1
Use Plasma pick power for +9
Now you have exactly one minute to:
Reset cooldowns by buying a pickaxe or spending 25 runic (kind of expensive...)
Equip Yogg's Tentacle
Click as fast as you can
Get thousands of every single resource from every single zone, including herobrine's lair, wasteland, and the aether.

Abilities that break blocks for you do not work:
Anvil gives regular drops only
Dynamite likewise.

Potions seem to have no effect. (Luck needs more testing)

Snowball seems best. If a creep spawns, lots of bonus blocks!

Hot Potato is also useful if used skillfully. (Timing is key, use it just after your 1 minute timer starts - do not click it, press the 1/2/3/4 shortcut keys!)

My other preferred skills and abilities:
Roll of the Block and Block Ankh (legendary drop) for even more random loot (Take care with stupid modal window popup, practice how to bypass it first, before you spend any runic)
Max out Pickaxe Fuel/Lighter for cooldown reduction and to extend the combo. (1 minute is still the max because of Plasma Pickaxe)
Mob Lure to increase the chance of bonus loot (from a creep spawning at just the right time)
Infinity scroll for the 4th ability slot.

Protip: Click in center of screen at first, then alternate between all your potential creep spawn points.

Do not kill a creep if it happens to spawn while setting up the combo, wait until Yogg triggers and pop it with a snowball.

The pictures are in my onedrive:
https://1drv.ms/u/s!Au8dVV9jd6UHgZj2W__uVglb3UCIQeo

C:\Users\Daniel3ICE\OneDrive\Desktop\5post+dyn.png
C:\Users\Daniel3ICE\OneDrive\Desktop\5pre.png
15132-8939 blocks broken = 6193
9696978875-5163600889 picks = 4,533,377,986

C:\Users\Daniel3ICE\OneDrive\Desktop\4pre1.png
C:\Users\Daniel3ICE\OneDrive\Desktop\4post2 +dynamite.png
(Oops)
8107551983-3747499885 picks = 4,360,052,098

C:\Users\Daniel3ICE\OneDrive\Desktop\3post2 +dynamite+creep failed to die.png
C:\Users\Daniel3ICE\OneDrive\Desktop\3pre.png
53976-47959 blocks broken = 6017
7995472747-3568633170 picks = 4,426,839,577

C:\Users\Daniel3ICE\OneDrive\Desktop\2post2 +dynamite.png
C:\Users\Daniel3ICE\OneDrive\Desktop\2pre1.png
7594-1445 blocks broken = 6149
51984093666-47546980794 picks = 4,437,112,872

C:\Users\Daniel3ICE\OneDrive\Desktop\1post2 +snowball.png
C:\Users\Daniel3ICE\OneDrive\Desktop\1pre1.png
75546-69342 blocks broken = 6204
5243664753-735803950 picks = 4,507,860,803

[3ICE]

In case you've not transcended 10+ times yet, my early game strategy can be found in my review:
https://steamcommunity.com/id/3ICEhu/recommended/734750/
It is similarly broken / powerful.

[҉҉S̷ῑF小狼҉]

It's already a decent guide.
I could confirm Luck potion and Potion of Beyond doesn't affect blocks that were spawned from Teleportal abilitiy.
I'd say instead of using "Roll of the block", use Block Ankh, It's far more useful. Especially if you use Enchantment / Snowball + Armoured creeps.
You seems to forgot that Lunar Pickaxe would give you +1 Block Fortune for 45 minutes.

Regards~

[3ICE]

Thanks!

Definitely adding Lunar pickaxe for its bonus +1 to the guide
Note: We can even wait out the 10 minutes pick power cooldown timer with this one, as it lasts conveniently long. No need to spend runic like with Plasma Pickaxe. And they do stack :)

Will mention Armored Creeps talent, and Enchant ability as well, good call. I used to run Enchant, but stopped for some reason. Maybe because too often I'd hit only dirt, clay, or sand with Enchant. Instead of books/thorium/aether/etc.
Will remove either Roll of the Block of Hot Potato for it. Keeping Ankh for sure :)
Teleport I still need to unlock.

Also ToDo for myself: Copy official wording from the game for things like categories and names on the talent tree. And abilities / buffs / effects / upgrades / etc. I messed up TNT / dynamite already, and who knows what else.

[҉҉S̷ῑF小狼҉]

If you wanted the official description of abilties and skill trees, you could copy them from the Gamepedia, they lacked a lot of stuff and probably outdated on a certain data, though.
Or alternatively you could use this link which contains summary of those stuff.
https://docs.google.com/spreadsheets/d/1jnkMN2xMRTDODi8ai59YkYaU_Io8qDgnNYRxq4CamJ8/edit?usp=sharing

Regards~

[Director Matchkin, the Imprinter]

...what about the drill ability? I recall it chainsawing through blocks fairly efficiently in the midst of Yogg's pickaxe power. As long as you're in the moon or earlier biomes, that is.

[3ICE]

Yes, definitely worth mentioning Drill, my highest level ability. But more research is needed: Does it increase yield per minute? Because there's a speed limit in the game and I'm already at it. I noticed no difference between my ability to click fast enough and the drill "helping". I already one-shot click blocks. I drill only when I lack PPS, e.g.: Ender pearl farming.

I've only used Drill 500 times for the achievement.

p.s.: I just unlocked Teleport! Hype!!