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What holds back most strategies is the multipliers.
Poison/ghosts gets an INSANE amount of multipliers. First the ghosts get a multiplier on damage, plus the item that boosts ghost damage, this is then multiplied by your generic bonus, then you have bonus poison items, hydras, herbalism, THEN your generic bonus AGAIN. This takes off when you unlock the bugs and the fast-click item. Summon hundreds of bugs which die automatically.
Bugs eventually fall off because they just don't die fast enough. For the final walls ~80+ you switch to maxing out the cultist summoner along with the "support minions get bonus" skill (or the skeleton summoner if you need to deal with pew pew lasers), unlock sorcerers and chain lightning (both just 1 skill point), and now you mass murder your own cultists by holding left click on chain lightning. Unlock additional sorcerers to further multiply your damage