Rock Band 3

This isn't hard and more often than not you'll get this by simply playing through the game.
Nevertheless it is usually easier to three star a song on Hard than five starring it on Medium if you are struggling with it. Because it is only 50 songs you can also ignore a good amount of them. Avoid the harder songs if you need to.
It doesn't matter which instrument(s) you do the songs with as at the end of every song you'll get a band score (even if you play by yourself) and that is what counts towards this.
Only Rock Band 3 disc songs count towards this!
The 'goal' is situated in Rock Band Mastery - Band Song Progress - Rock Band 3 Medium Master
NOTE: If you are playing as a band, you must all be at least on Medium to get it to count towards this.

However, if you jump around from instrument to instrument playing this game, and play usually by yourself . Then voila! A list of every song in the game and what the game (or in the case of the same difficulty, the global leaderboard) says is the easiest instrument to play it on! You don't have to take these to heart, you are going to be better at one instrument than others and will probably play the songs on different instruments than the ones I stated.
"20th Century Boy" - Drums
"25 or 6 to 4" - Vocals
"Antibodies" - Vocals
"Beast and the Harlot" - Vocals
"The Beautiful People" - Keys
"Been Caught Stealing" - Bass
"Before I Forget" - Vocals
"Bohemian Rhapsody" - Drums
"Break on Through (To the Other Side)" - Vocals
"Caught in a Mosh" - Vocals
"Centrefold" - Drums
"China Grove" - Guitar
"Cold as Ice" - Guitar
"Combat Baby" - Keys
"The Con" - Keys
"Crazy Train" - Vocals
"Crosstown Traffic" - Drums
"Dead End Friends" - Vocals
"Don't Bury Me...I'm Still Not Dead" - Bass
"Don't Stand So Close To Me" - Drums
"Du Hast" - Bass
"Everybody Wants to Rule the World" - Guitar
"False Alarm" - Vocals
"Fly Like an Eagle" - Guitar
"Foolin'" - Drums
"Free Bird" - Vocals
"Get Free" - Guitar
"Get Up, Stand Up" - Guitar
"Good Vibrations" (Live) - Guitar
"The Hardest Button To Button" - Guitar
"Heart of Glass" - Keys
"Here I Go Again" - Bass
"Hey Man Nice Shot" - Drums
"Humanoid" - Bass
"I Can See for Miles" - Bass
"I Got You (I Feel Good)" - Drums
"I Love Rock N' Roll" - Bass
"I Need to Know" - Drums
"I Wanna Be Sedated" - Vocals
"Imagine" - Bass
"In a Big Country" - Drums
"In the Meantime" - Keys
"Jerry Was A Race Car Driver" - Vocals
"Just Like Heaven" - Bass
"Killing Loneliness" - Drums
"The Killing Moon" - Keys
"King George" - Vocals
"Lasso" - Drums
"Last Dance" - Guitar
"Living In America" - Guitar
"Llama" - Vocals
"The Look" - Vocals
"Low Rider" - Guitar
"Me Enamora" - Guitar
"Midlife Crisis" - Guitar
"Misery Business" - Guitar
"Need You Tonight" - Keys
"No One Knows" - Vocals
"Oh My God" - Keys
"One Armed Scissor" - Bass
"Outer Space" - Drums
"Oye Mi Amor" - Bass
"Plush" - Drums
"Portions for Foxes" - Vocals
"The Power of Love" - Drums
"Radar Love" - Keys
"Rainbow in the Dark" - Keys
"Rehab" - Guitar
"Rock Lobster" - Keys
"Roundabout" - Vocals
"Saturday Night's Alright for Fighting" - Vocals
"Sister Christian" - Bass
"Smoke on the Water" - Guitar
"Something Bigger, Something Brighter" - Vocals
"Space Oddity" - Vocals
"Stop Me if You Think You've Heard This One Before" - Drums
"This Bastard's Life" - Drums
"Viva la Resistance" - Bass
"Walk of Life" - Drums
"Walking on the Sun" - Drums
"Werewolves of London" - Vocals
"Whip It" - Vocals
"Yoshimi Battles the Pink Robots Pt.1" - Bass