Took a few run throughs but finally made a very simple guide for recommended order of challenges, upgrade choices, and booster/manifold numbers.
https://docs.google.com/document/d/1Tg01KHz-TjXISXjXIz5HGYG3bYIqpPuz3gjth2VzWAw/edit?usp=sharing
Tip for those starting out, when you get your first booster buy the first upgrade. When next you hit infinite just hold down the 'I' and 'M' keys to get your next few boosters.
Tip for those stuck around the mythos 1e70. Farm offerings by doing 1800 second trandscend runs, you should be able to level up a rune each time and slowly progress that way.
For those of you having trouble use the slow-mo skill, it can basically be used non-stop. Using it I beat the emperor without taking damage and the second to last level was a breeze.
For challenges 1-3 on epic you need is max shield and max altar (mana). Once your mana is maxed at 400 charge the castle and keep invincible up. It lasts for a little over 45 mana, so casts would be at 400, 365, 330, 295 etc. For the last challenge you don't get the chance to store mana, so leave your heroes behind and charge the castle, all your troops should be enough to stall the monster until you can store up mana.
*Note you do not need and I advise against using titans with this strategy.
 "Ordinal Markup"){kind=icon}
 "Synergism"){kind=icon}
 "GunBall 2: Emperor Revenge"){kind=icon}
 "Epic War 4"){kind=icon}