Pretty much too broad of a question to answer, but here's my best shot. First, anything that has its roots primarily outside of video games I think should be disqualified, that kicks out any comic book, movie, or television show characters. I'm also defining "Most powerful" as, able to overcome any situation. Lastly, anyone who can be outright permanently defeated can't be the most powerful. Which means I have to go with, The Prince, from the Prince of Persia series for his ability to rewind time and redo everything until he gets it right the first attempt.
True, your heavy hitters like Kratos can fight their way back out of Hades, or Alex Mercer seems to just keep coming back, but they are still beaten long enough for whatever goal they were attempting to achieve or event they were trying to prevent has passed them by or been completed respectively. Where as, the Prince always gets it right the first try, well the first try that counts as far as history is concerned.
Time manipulation is always the best trump card.