Yeah but you have to show how they break up in the first place so you'd need a good 30 minutes of MJ... also I don't know if Lizard is the perfect villain to go along with a break up... SM3 was the perfect time to do it... it can still be done... but yeah that only seems logical at this point... I would consider not having MJ in SM5 entirely.
The Lizard is the PERFECT villain to cause Spidey and MJ breaking up. Here's how:
You have some time pass since the last movie and Pete and MJ aren't technically all the way back together. The ending of the last movie was kinda left open, they didn't seem too happy to be dancing together.
So MJ says to Pete that she really DOES care about him and can't keep worrying about him dying or getting seriously hurt as Spider-Man. She wants to meet one night to talk over dinner about their relationship or something. Pete is totally willing to do it, he loves MJ and wants to work things out, and he tells her this over the phone, but he's also HONEST and tells her that he has to go see Doc Conners (Pete's his lab assistant) that night because Conners wanted to tell him something, but Peter is going straight to dinner right afterward. They agree to meet at eight.
Pete goes to see Conners, who's in a competition for a huge grant with another fellow professor, Adrian Toomes. Toomes, of course, is a scumbag, and sabotages Conner's formula (to grow back human limbs) and Conners doesn't know. So when Peter shows up Conners is excited to see him and tells him that his formula will work and is going to show him. Pete asks him to reconsider (thinking about what happened last time a scientist he knew didn't wait to get proper human trials, The Green Goblin happened), but Conners is convinced it'll work. So it does for about five minutes and then Conners transforms at night, in front of Peter and no one else.
Obviously Spider-Man has to try to help Conners and as he's on the school roof putting his mask on, he looks up at the big campus clock--8 o' clock. He missed his date, but he had to, because your mentors don't turn into giant savage lizards every day. Plus, Spidey gets the crap beat outta him, and barely survives the fight long enough to get back to his apartment and pass out for the whole night.
That's how the Lizard lends himself to a great story involving Peter and MJ breaking up.