The puzzle is presented as a series of groups of mini-puzzles. Each group can be solved using techniques from one of the headings in the ACME Have You Tried document:

What is it? (3)

• …Braille: THE LETTER AITCH (H)
• …using the Library of Congress system: THE SCARLET LETTER (A)
• …getting on the T: Draw lines connecting the three stations to form a letter (V)

Letters and words (14)

• …determining if it is a Rot 13: THE BEGINNING OF ETERNITY AND THE END OF TIME (E)
• …rearranging the letters (“anagramming”): THE LETTER THAT PRECEEDS ZED (Y)
• …looking at a computer keyboard: The letters form a circle around a letter (O)

Numbers (1)

• …treating numbers as latitude/longitude: Draw lines between the coordinates to form a letter (U)
• …matching numbers to MIT buildings: The three named buildings form the shape of a lettter (T)
• …treating numbers as radio stations: The call signs for the stations all end in the same letter (R)

Thirteen ways of looking at a puzzle (10)

• …connecting the dots: THE LETTER BETWEEN J AND H (I)
• …looking at it in a mirror: THIS ONE IS THE LETTER E (E)
• …saying it out loud to someone else: I’LL SAY THAT YOU WANT TO TAKE D AS THE NEXT ONE (D)

Numbers (2)

• …seeing if prime numbers are involved: The 20th prime number (71) is missing (T)
• …treating numbers as ASCII numbers: ONE OUGHT OBTAIN ONE OH (O)
• …graphing it parametrically: Graphs a circle above a rectangle, for a lowercase letter (I)

For starters (4)

• …typing it into a search engine: The first hit from Googling these words is “The Letter N Song” (N)
• …reading the title and the blurb: The puzzle’s blurb says how to interpret a double asterisk (D)
• …pursuing a train of thought: The missing railroad from Monopoly is READING RAILROAD (E)

Zen (2)

• …asking for fresh brains: The victim is dead, so the eyes are crossed out (X)
• …thinking about what’s missing: One letter is missing from the pangram (I)
• …trusting someone else’s instincts: (N)

Thirteen ways of looking at a puzzle (10)

• …tilting it: Looking from the edge of the screen, it says TANGO (T)
• …folding it: Fold the light lines together so they touch; it says THE LETTER YOU SHOULD USE IS INDIA (I)
• …looking at it upside down: The text clues TEA (T)

Numbers (3)

• …treating numbers as atomic weights: Drawing a line between the elements on the periodic table forms the shape of a letter (L)
• …seeing if fundamental constants are involved: This is Euler’s constant (E)
• …using it as a phone number: On a phone, these form the shape of a letter (S)

Once all of the mini-puzzles have been answered, the extracted letters read HAVE YOU TRIED TO INDEX IN TITLES. Using the numbers in each section of the puzzle to index into the corresponding section of the Have You Tried document:

Reading in order yields the answer, AD NAUSEAM.