What would you do, if you knew everything? Where is the line, the limit to how far you can go? That is the idea of the movie, and then the TV show, Limitless. Many people talk in forums and gaming magazines and even in tabletop groups about turning movies into RPG adventures, and I think Limitless has the potential to be such an example, best seen by the fact it even got a TV series, which shows it has continuing stories to tell.
The first thing is that this movie is a perfect example on what you can do with knowledge skills. In the movie, the protagonist goes from being a socially handicapped slob unable to finish a book skating through life all the way to a socially well adjusted, multi-lingual, rich, best selling author and political figure who seems to know everything. He is no stronger, no faster and likely no handsomer than we was before, just his mental attributes increased and he becomes essentially a social chameleon. In the TV show, the first episode has a similar down on his luck nobody who then with the same drug becomes able to prove his innocence by the connections of various points he is able to make.
The first time the pill kicks in in the movie shows it shows how it pulls various bits that he had seen from anywhere in time and serves it to him for immediate use. The combat scene in the movie shows how his combat skill isn’t an enhancement to hi physical being, but instead his understanding of how to fight has changed. The TV series uses an example of ‘What if you knew exactly how much strength you had in your hands’ as a way to calculate an escape route, as seen in the trailer, not to mention calculating a safe path to run across the street or exactly where a subway train would stop as part of an escape. These things are sometimes things players will bring to the table, trying to use their knowledge of how things work in the real life as a way to approximate their working in your game world. Sometimes you decide that it works for them, other times, you may want to judge them as not the same because the PC does not possess the skills to make the decisions.
Other examples of this sort of power can be seen in other sorts of media. One is in William Gibson’s Bridge Trilogy, with a character who has a mental ability to see connections and how those connections fit together and lead to certain outcomes, predicting the future by the shadows left in the past choices. Sherlock shows this trait in all his stories but especially in combat in the movies, predicting how opponents will react and the outcome. It is almost like Action Man in the animated tv series, predicting things by analyzing the scene for the best outcome. The Pretender was a show where a person would pretend to be someone to correct some injustice like someone getting away with murder by using his talents to fit in anywhere, and then there’s John Doe who knows everything about everything except himself. Various sorts of stories you can see about how knowing everything can be.
To challenge the skill-monkey sort can be hard, especially if they are the type to sacrifice combat abilities for more utility options. You can make a number of various challenges like fallen bridges, lost trails, or even having to get out of a situation with nothing but a paperclip, and if the player comes up with a reasonable use of the skills to fix the problem, let it have a chance. Also, there can be combats but it would be groups that are focused on other things in most cases. Stopping the player is more of a delaying tactic while they solve a goal somewhere else, like if you look at Indiana Jones and the Raiders of the Lost Arc, they had a few quickly resolved fights in the marketplace as their goal was to get the items and get away. That way, if the player is losing the fight, they can use delaying tactics to survive until the enemy goal is complete.
One type of plot these characters are great for is mysteries. Listen to their theories and adapt them to your story, since they may be more complex than what you had and the player will feel special for having guessed beyond their means. You can use this in different ways from the standard theft or murder detective stories all the way up to massive conspiracies. These give the players ways to investigate, try to figure out various things and how they relate to their predicament.
The key to running for someone who is skill based is to have some idea as to how all their skills work and be willing to work with the player as to making them work in game. Have them use science to deduce where a specific patch of dirt came from, as Sherlock Holmes could identify them on sight. There are all sorts of skill usage that can be fitted investigating or examining the situation, if given enough thought. If you need help, just ask.