Here are some useful tips for mephisto's missions (might take some time mastering them all of course)
1) Most of the enemies respawn twice, the exceptions are the fire giants that have no limit of respawn if you go back and forth in the stage and return to the place they appear the first time. I DO NOT recommend increasing your scores by killing multiple giants, because you'll lose precious time
2) Every hero has a very useful power for fast kills (I'll list them in the order they appear in the pc version. Sorry but I don't remember their names)
Use his 6th power as much as you can. Fast movement and quick striking is very important to progress in the stage as he lacks of an instant kill attack (except his blood haze xtreme probably)
His 7th power is a must. His freezing aura is quite useful to deal dmg to surrounding enemies while you are fighting another one. Also with that boost you'd like to let the demon leapers to jump into your back as that will kill them instantly
. As for enemies that are far away or are approaching I like to use the freezing ball attack he launches, while I like the combining both 6th and 7th powers to take out fire giants.
His 5th power is awesome to eliminate foes. Converting opponents into crates with an instant kill + heal/energy recovers from destroying the boxes is very useful. If you have trouble keeping him alive, I'd suggest using royal seer attire
His 5th power also works great vs demon leapers. When you are using that flamethrower whenever a leaper jumps into your back it will also deal an instant kill.
3) Your stronger attacks are performed with the giant's sword. Try to weaken him first so you won't waste sword attacks on him. Also, DO NOT KILL THE GIANT WITH THE SWORD STEALING MANEOUVRE, that would likely trigger a bug and the sword won't work despite being in your hand. Be careful with iceman as his freezing aura may also kill the giant accidentally and the sword stealing won't work. In the case of the 2nd giant, his sword has better use against the boss, so leave him to the last, steal his sword, kill him, go to the boss fight, use one of the temporary boost powers and skip dialogues fast so you can hit him hard from the beginning.
4) From the bridge part onwards, throwing enemies to their deaths is also a great method. Remember Dr. Strange's 2nd power, it makes it easy to throw enemies.
5) The boss fights. Of course the easiest wins come when the boss-doing-nothing glitch occurs (and I remember one time dark spider-Man fell to his death lol). Fire sword attacks will damage Baron Mordo a lot, specially when Dr. Strange is using it (idk why).
The rest is mainly try to deliver easy damage with ranged attacks and keeping your distance when freezing attacks are going to be used. Against Dark Spider-Man just attack as fast you can, I don't think there is another easy way to win with blade.
6) If you still have trouble (which is possible, I remember I needed lots of attempts to improve my movements and power timing) equipping spider bite should help. Also memorizing enemy respawns is useful so you can kill them all in your way towards the boss (except the infinite giants of course)