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I personally haven't gotten past Ascension 5 but I'm sure there will be times when those bigger swings in numbers will come into play.
One of the better uses for the One Die is to change certain keywords. Evolve, Loaded Ammo, Kicker are very good, but *any time* a dice uses a low number for an effect it's very strong.
There are some low-dice strats, but it's a decision you want to make depending on your run. My first victory was with a d8, and that's because I was panicking and using it to punt down my Injury stacks.
Secondly, even with the largest possible die - d20 - you can always use dice cheat min\max or good\bad luck to get the lowest or highest possible roll. Still, a bigger die is almost always better - a modified relic can be a game changer.
I had a run yesterday where I had a bunch of Curse cards, which I was able to paint blue at an event tile. VERY OP.
Was able to modify the [Drumstick] relic to heal me for 15hp every time I lost hp, but only 12 times per combat XD
You generally want higher numbers on your cards, relics, events and money, there are exceptions, but not many.
Perhaps even more useful is editing relics directly, though. Putting high numbers or high die sizes onto relics that balanced around low numbers or d4’s/d6’s on their effects is crazy good. All cards in your hand sharing a color gives you two power each turn? Let’s make that 7 instead. Every time you break an enemy’s hp bar, you get d4 temp power and d4 block? How about if both of those were d12’s. The possibilities are huge, and seem to me to be way more numerous and (on average) more powerful than those you get with a small die.
Buying in a shop? Drop the prices - that's every bit as good as having more money.
Trying an event? Drop the DC to guarantee or near guarantee success. Drop the sacrifice costs in HP, money or max HP.
The one area that a big dice is clearly superior is upgrading the numbers on cards and relics. The drawback here is curses/distortion, combined with the opportunity cost of all the one dice upgrades in the first place. Any individual decision is a tradeoff that puts pressure elsewhere. It absolutely works, but you probably have to devote resources into cutting extra bad cards or circumventing distortion effects from your deck to get there.
Rerolling relics choices is definitely better with a D12 than a D6, but the reality is that it just saves dice charges. The average of rerolling twice with a D6 is about 5.85 new relics to see, compared to 5.95 with a D12.
To be fair, none of it matters that much as the game is extremely easy either way, and perfectly playable without using the one dice at all, or just minimal amounts on high ascensions.
GO TEAM HUGE DIE!!!!