D.Va is the only character in the game who has more than one life, one must always take into consideration that destroying her mech won't be enough to stop her outright, although it will put her out of commission for a little while, she can still get it back. D.Va's most effective move is her Defense Matrix, so it's best to work around it with abilities that go through it (like with Zarya's Particle Cannon) or outright disable it (such as Sombra with her Hack).
The Endothermic Blaster's primary fire is not negated by Defense Matrix, meaning Mei can get rid of D.Va's protection ability and make it easy for her team to destroy her mech. In Pilot form, D.Va gets killed by 1 headshot from Mei's secondary fire. Mei still needs to be wary of Suited D.Va, as she can negate Blizzard with Defense Matrix if the drone hasn't touched the ground after being thrown.
Sombra's Hack will disable D.Va's Defense Matrix and Boosters, limiting her chances at survival since she can no longer defend herself nor escape. Since Sombra's Machine Pistol has a large magazine and deals considerable damage when up-close, it is possible for her to kill her entire mech in one clip given the large hitbox it has. Sombra's Hack will also pass through D.Va's Defense Matrix.
Symmetra's Photon Projector will pass through D.Va's Defense Matrix and continue to build up in damage which will eventually destroy D.Va's mech or force her to use her Boosters to escape. Her Sentry Turrets will also deal damage to D.Va while her Defense Matrix is up and it will slow her down in the process. In addition, she can use her Photon Barrier to protect her and even her allies from D.Va's Self-Destruct.
Zarya can gain good amounts of energy from D.Va's Fusion Cannons, not to mention her Particle Cannon's primary fire pierces through Defense Matrix, and can easily hit Suited D.Va because of her large hitbox. Even without a barrier available or with low energy, Zarya can pose a threat to D.Va because the latter's limited range allows the former to back up while still dealing damage. Zarya's Particle Barriers can be used to shield herself and her allies from D.Va's Self-Destruct. Keep in mind that Defense Matrix can delete Graviton Surge's projectile.
Ana loses both her self-defense options and her ability to heal if D.Va holds Defense Matrix in front of her. Ana also suffers in close-quarters combat, and doesn't do much damage to her mech due to its armor.
D.Va's Defense Matrix can absorb any and all of McCree's offensive abilities, including his ultimate, rendering him useless. His Peacekeeper is effective at taking her out from a distance, but will be somewhat ineffective in a close encounter. Overall, D.Va's ability to nullify his attacks and large health pool make her a suitable counter. Should he try and escape using Combat Roll, D.Va's Boosters can be used to close the gap between them.
D.Va can use her Boosters to either reach a higher platform or get into Pharah's face and continue damaging her if she attempts to outrange her. Additionally, Pharah's entire Barrage can be absorbed by D.Va's Defense Matrix. If she is in the air when D.Va uses her Self-Destruct she will likely die since the blast deals damage to enemies in all directions within 20 metres.
Since D.Va's Fusion Cannons hold unlimited ammo, she can continuously fire at Reinhardt's Barrier Field until it is destroyed. If Reinhardt is close enough, his Rocket Hammer will only deal 75 damage through D.Va's mech which won't be enough to match D.Va's Fusion Cannons. She can also use her Defense Matrix to absorb his Fire Strike. He can block her Self-Destruct using his shield but doing so will put his shield down to half health which can then be followed up by D.Va's Fusion Cannons
D.Va's Defense Matrix is a major problem for Roadhog, as it can prevent him from killing targets reeled in by his Chain Hook, and is also able to negate up to 4 seconds of Whole Hog, meaning he is very vulnerable should he decide to use it while she still has her mech. While D.Va can be hooked to temporarily stop Defense Matrix, she is still a problem to him if Roadhog's teammates don't focus fire towards her.
D.Va is able to negate all of Soldier: 76's damage with her Defense Matrix, allowing a teammate to easily finish him off, and will usually win in a 1v1 fight against him due to the knockback from her Boosters knocking him away from his Biotic Field. Her Defense Matrix is also a strong counter to Tactical Visor, as it will negate most of the damage done in its duration.
Widowmaker's scoped shots can easily be blocked by D.Va's Defense Matrix. In addition, D.Va can use her Boosters to close the gap between them if she is far away or attempts to escape using her Grappling Hook. Her automatic fire will not be able to deal enough damage to D.Va up close to prove any kind of threat given how massive her health is.
Although Tesla Cannon passes through Defense Matrix, D.Va's high armor and overall HP means Winston will have a tough time breaking her mecha. Because of his large hitbox and head hitbox, D.Va's Fusion Cannons will hit most, if not all of their pellets and deal hefty damage. If Winston decides to leap away, D.Va can use her Boosters to chase him down and confirm the kill. It is important to note that Winston can use his barrier to restrict Self-Destruct's area of effect.
Bastion's very high fire rate and large ammo count in turret form means that even though D.Va has a large health pool, it can easily spam and still have enough shots to finish her mech. Also, due to D.Va's very large hitbox, most of its shots will land. Despite this, Defense Matrix will stop all of Bastion's damage for a period of time, even from Configuration: Tank. If Bastion has teammates such as Orisa supporting it nearby, D.Va will effectively shut down multiple enemy team members for a period of time, allowing her own team to quickly gain the lead.
Genji's Shurikens are capable of dealing big damage to D.Va's mech while her Defense Matrix isn't up. He can also use his Deflect to deal some damage back to her and his Swift Strike and Dragonblade will deal damage through her Defense Matrix. However, D.Va's Fusion Cannons hold unlimited ammo and she can continue firing at Genji while he is moving, and damage from her Boosters isn't blocked by Deflect.
Junkrat's explosives will deal big damage to D.Va's mech and he can easily hit her thanks to her large hitbox. However, keep in mind that anything he throws at her can be absorbed by her Defense Matrix, except for his RIP-Tire and his Steel Trap. The former will deal enough damage up close to instantly destroy D.Va's mech granted she doesn't destroy it before it reaches her, and the latter she can easily survive the duration of using her Defense Matrix. but will still be trapped and not of much use.
Reaper's Hellfire Shotguns deal devastating damage up close, but Defense Matrix prevents him from doing any damage. If D.Va doesn't have Defense Matrix available, Reaper can quickly kill the mech due to its large hitbox and The Reaping helping him survive. Both of them can survive the other's ultimate ability: Wraith Form to survive D.Va's Self-Destruct, and Defense Matrix to absorb Reaper's Death Blossom.
Although D.Va may be somewhat of an easy target for Tracer, her Defense Matrix gives her a good chance of survivability and it can be used to absorb her Pulse Pistols as well as her Pulse Bomb. Her Fusion Cannons can be effective against Tracer as long as she's good at adjusting to her Blink. Tracer can very easily escape Self-Destruct by using multiple Blinks or Recalling at the right time.
Because D.Va doesn't need to reload, Mercy can damage boost her to increase the power of her constant fire to great effect. Mercy can keep up with D.va's Boosters via Guardian Angel, and can benefit from her high health pool to build Valkyrie faster.
Reinhardt can use his Barrier Field to protect D.Va if she chooses to flee using her Boosters or if her Defense Matrix runs out. He can also use it to protect her from Zarya's Particle Cannon and allow her to have the upper hand. Lastly, Reinhardt's Earthshatter will stun everyone allowing D.Va to get multiple kills with her Self-Destruct. He can also pin an enemy Reinhardt with Charge in order to drop his shield and leave his team vulnerable to Self-Destruct.
Sombra can hack high value targets for D.Va such as Mei or Zarya which will make killing them a lot easier. It will also mean they will not be able to protect themselves if D.Va chooses to use Self-Destruct. She can also use her EMP to disable all enemies' abilities and leave them with no means to escape from D.Va's Self-Destruct.
Tracer and D.Va make a great pair. Both have comparatively high mobility, useful for rushing through enemy defenses and wrecking havoc, and have a great damage output, especially Tracer. They also have very destructive ultimates.
D.Va can use Boosters to dive in with Winston to wreak havoc, and her Defense Matrix offers him protection from threats such as Roadhog and Reaper. When diving together, the two can quickly kill a key target and flee rather easily.
Zarya can apply a Projected Barrier to D.Va when she attacks, allowing her to conserve Defense Matrix charge. Their ultimate abilities also combine well. D.Va's Self Destruct, if positioned and timed correctly, will eliminate all opponents trapped inside Graviton Surge due to their lack of escape options, as well as Self-Destruct's massive damage. This combination is an all-or-nothing type, as Self-Destruct will kill enemies even if they're protected by Transcendence and Sound Barrier, but combining the two ultimates requires good timing and positioning to be effective, because Graviton Surge can run out before the mecha explodes. Keep in mind that Barriers make this combo near-useless.