Ancient Cave mode completely changes how the game is played. Instead of proceeding through the normal storyline of EarthBound, all rooms and doors have been shuffled around into a multi-level maze. You start with all four party members, and your goal is to proceed through all 8 levels of the maze, each level guarded by a Shiny Spot, and reach and defeat Giygas.
Keysanity mode also radically changes how the game is played. 15 different key items have been shuffled around throughout the world; Mayor Pirkle may give you the Bicycle, while the Bike Shop guy may give you the Carrot key. To help you on this more complicated quest, however, Ness already knows PSI Teleport, and all available teleport locations are unlocked at the start of the game (including bonus teleports to South Winters and North Onett). Your goal is to beat the game as normal, but getting to all 8 Your Sanctuary locations will be more of a challenge.
This is the normal mode of playing EarthBound. Only the flags that you set below will be changed. Otherwise, the goal and playthrough will be similar to the vanilla game.