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You can use 10 tokens (presuming you have everything unlocked already) On the statue to the left of the abyss entrance to get a random relic or two for the start of your run.
Id highly suggest going for athena if you are trying to get to nightmare difficulty.
Player is up to you, i did it with the default first character because i liked the starting bomb and key.
Try and do most rooms hitless and save any heart pick ups for the laser heart room, there you can sacrafice hearts for coins on the floor, and every 7 or so times you do it, it will turn all the coins in to something random, so if you get a roulette machine in there, then repeat the same thing with the hearts, you will get a lot of money keys bombs and even some relics for your run
If you get a bad relic and shop room on the first floor along with a crappy boss drop, you can restart since your just on the first floor, but you will loose your free items from the beginning sacrifice,