Mysterio is a cyclical character with all three of his colors, and you’ve got to plan around that (he’s not like, say, 3* Gamora, where you can take her into a match for her cheap red and not care about the other two powers).
Blue passive converts blue AP to yellow, with a nice bonus stun/damage if you have excess blue.
Yellow active converts your yellow matches into purple AP while a countdown is active, with the (weird) disadvantage that he steals ally health when that countdown goes off. Upside is that the blue passive feeds this power, so you can keep gaining yellow AP to keep the countdown on the board even though your yellow matches are generating purple AP.
Purple goes invis and drops some blue traps that are your main source of damage. These go off when matched OR destroyed, and conveniently are the same color that you want to match to start building up blue AP for his passive to begin with.
So, first thoughts. Obviously works well with Red/Black/Green characters. He would work well with people who have passives in his colors that don’t interfere with his cycle. He would work well with people that generate tiles and AP in his colors. He would work well with characters that destroy tiles and can set off his traps. He would benefit a tiny amount from someone who could make him invisible to keep his trap damage higher. And he could theoretically benefit from playing support and using part of his cycle to feed other characters (say, using his blue/yellow to generate purple AP for another character).
I like 4* Carnage, colors are completely separate, Carnage does his own thing with his black passive, and Carnage’s green can destroy those traps. Mostly two separate sources of damage with some mild overlap via Carnage’s tile destruction.
4* Iceman can be interesting. Mysterio uses blue and yellow to make purple, Iceman uses purple to put down more blue, Iceman uses green for an AoE nuke. If there aren’t any red tiles for Iceman, you can put down Mysterio’s traps with purple, and you’ve got Iceman’s stronger blue stun up your sleeve. Gives for a little versatility.
Sandman can give a stupid amount of board shuffling. Get Mysterio’s countdown out, start using Sandman’s purple, shuffles the board, makes yellow tiles, any that are matched become purple thanks to Mysterio, and Sandman can keep shuffling the board. You get Sandman’s decent green, and don’t worry about his yellow.
Really, while you can make some kinda fun combos, Mysterio would probably be best paired with some goons, as an enemy in a PVE event, where two Maggia type dudes can make blue/yellow AP to fuel Mysterio and make him more dangerous than he would be without that AP generation. His kit just isn’t quite fast enough, and his damage not quite high enough, to make him really shine on his own. You can make him work if you’re having fun trying out different characters, but he doesn’t really work in a competitive sense. For Essential nodes, you’re just as well off taking two characters he’ll interfere with least and letting them do the legwork.