To prevent migraines and headaches, I have a simpler solution then what others have posted on here for this achievement and I'll show you how:
1. First, go to the main menu options. Then go into In-Game Options and put the difficulty to Easy, Kick Out System: Tap/Hold, Reversal Damage: Off, Stamina System: Off and Blood is up to you but for realism I always keep it "ON" in every WWE game. Now hit A to accept.
2: Next what you'll wanna do is go into GamePlay balance options. Now go into A.I Reversal Balancing, turn everything to low (Slider left) Now for damage balancing and game balancing, put both of these settings to the maximum to make it easier on yourself and to make this go quicker then normal.
3. Now go back to the main menu, go to create modes and then select story designer, select new. It will then take you to story designer, skip the tutorial as that's not needed for this achievement or any. Now Hit the first option highlighted of the week, Monday Night Raw then hit add Match "NOT" scene then hit Match Type, Put a Six Man Battle Royal on and choose Rey Mysterio as yourself, "The User" and choose Santino as "Com" and choose 4 others, best to look for low overall ranking superstars such as Primo, The Miz, Matt Hardy etc but it's up to you as we have an advantage already because of the A.I Reversal Setting changes.
4. Once you have chosen your four superstars Hit Y and put everyone's Health down to nothing, (Head, Body, Arms and Legs all to 0%) once done hit accept. Now go to Match Conditions put the Difficulty to Easy, Arena can be left on default, Start The Match Immediately to Off and Victory Scene to Off as well. Now go down to Match Rules and put Entrances Off, Momentum Bar Charge Speed to Fast then Hit A. Now put over the top rope to "Off" then hit A it will take you back to the previous screen hit accept and now the match and all the settings are created.
5. Now on the Match you just created, Hit A, go to Copy/Paste and hit A on ADD, it should say, "Copy the selected moment to this location?" Hit Yes and now it will of copied the match we just created to a new slot, do this 50 + Times so that you will have enough matches to play and get it in. They may not all be required depending on how many times you have pinned others with a grapple pin either randomly or on your doing.
6. Now Hit X to preview the story. It should say something along the lines of, "In order to PREVIEW, you must save the Created Story first. Save Story and PREVIEW? Select Yes, give it a name and save into a empty slot.
7. Now once the match starts, Beat on your badly damaged opponents till Mysterio has his 619 that finishes with a pin move. when he goes for the spring board off the ropes it will prompt you to hit (B) to pin or you can use Mysterios other grapple pin move when Santino is groggy. Just run behind him and hit up on the Right stick to do a flip move which will also prompt you to hit (B) get the 3 count. You will win instantly. Repeat till you get your 50 wins.
I didn't do every match in Story Designer as I thought it wasn't unlocking so I went to 1V1 against Santino as Rey and after a few rematches it unlocked so I can wholeheartedly confirm it works through Story Designer. I was just being impatient. I hardly did that many before attempting this "Story Designer" method.
The Story Designer method also works for many other achievements such as, "Thank You Shawn" Defeat Shawn Michaels in the WrestleMania arena on Legend difficulty as The Undertaker (Offline). For Whom the Bell Tolls: Pin or submit The Undertaker in the WrestleMania arena on Legend difficulty (Offline). "Talk About Resilient", Kick out of The Undertaker's Tombstone Piledriver finisher on Legend difficulty (Offline). All you have to do is change the Difficulty on the Story Designer settings to "Legend" and you're good to go. This will also work for nearly every other achievement for SmackDown Vs Raw 2011 apart from "WWE Universe" and "Road To Wrestlemania" based Achievements.
I hope you will find this solution helpful and if so, please give it a positive thumbs up. If you can't get it to work or somehow don't understand this guide then just do what others have been saying and start a 1V1 match as Rey against Santino and Beat on your opponent till Mysterio has his 619 that finishes with a pin move or when he goes for the spring board off the ropes it will prompt you to hit (B) to pin or you can use Mysterios other grapple pin move when Santino is groggy. Just run behind him and hit up on the Right stick to do a flip move which will also prompt you to hit (B) get the 3 count like I said earlier then just keep rematching. This way will take longer but is still doable. This Achievement does not have to been done in one sitting thankfully unlike a few of TNA Impact's Achievements.
ENJOY AND PLEASE DON'T LEAVE ANY NEGATIVITY WITHOUT SAYING WHY FIRST!