I still remember fighting Psycho Mantis in Metal Gear Solid 1. He would read all your moves before you did them and was literally impossible to beat. He would also talk to you about the games that you had already played by reading your memory card (this was super trippy). The only way to beat him was to unplug your controller and plug it into port two so he couldn't read you moves anymore. It took me and my buddy days to figure it out... This was before Google too, so you couldn't just look it up.
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i would have to say omega himself, it took close to an hour at my level. then there was jormungand in the arena conquest, ***ING JORMUNGAND! my lawn, my lawnmower ahh, dr. nefarious on hard difficulty, not even the best weapon (at its starting level), best armo in the game would make a dent or prevent some of the damage