First, ignore the name Champions Online:
It maybe called Champions, some Champions characters appear (no Seeker though), you may see some familiar looking words like STR, DEX, ED, PD. But they don't mean squat. They don't work like in PnP. It's worse than DDO, which at least used the 3rd Edition system as a base and the deviated. They didn't even try here.
You build Mana up:
Mana, Endurance, Stamina, whatever you want to call it, don't think of it like a traditional MMO. Think of it like a Rage or Aggression bar from a fighting game. Every character starts with an Endurance (End) Building power, and End Building can be added to other powers (this is called Accelerated Metabolism). You build End up, and then expend it using other powers.
Also, End isn't always End. You will see End and Energy used interchangeably in the game, both referring to the same thing.
You can only have 1 passive power and 1 block power active at a time:
You can take multiples and as you level you can create multiple “Builds” based on the role you will play in a fight, but only 1 passive can be active at a time. This maybe the feature I hate the most, as it really stops you from building a quality tank. It also makes you waste powers. By level 20 you will have your character built, 1 End builder, 1 powerful melee attack, 1 powerful ranged attack, 1 AoE attack/Nuke, 1 travel power, 1 primary defense, 1 block power, and 1 click buff. You may sub out some Crowd Control or Healing or extra buffs and debuffs. So, you now have 20 levels worth of additional powers to take, maybe you would want to fill those out with say some Regen or Damage Mitigation or additional block abilities. You can get them, but you can only use one at a time. So if you have a block that works well against Energy and one against Physical, you better know which will be better before the fight starts, because you can only use 1 and you can't switch on the fly thanks to the build systems cool down timer. Got both Invulnerability and Regeneration, only get to pick one at a time.
Memorize where the “Z” key is:
You will use it a lot. Pressing the “Z” key while an enemy attempts some kind of CC on you will help minimize it's effectiveness. Also, the “Z” key is the default interaction key for world object and NPCs. Don't hit it too much though, you can skip things you need by doing that.
Problem is, if there are multiple things around you that can be interacted with, the Z gets confuzzled. Was that bad guy hitting you with a hold and you were pressing Z to resist it, but a park bench was nearby? Too bad, you are now held holding a park bench over your head.
Know what BAM, BOOM, FOOM, KABOOM mean:
You will see these word appear over enemies' heads as they charge up major attack powers. Actively Blocking (hold SHIFT) when these attacks go off significantly reduces the damage you take.
BANG: Single Target Attack
BOOM: PBAoE Attack
FOOM: Cone AoE Attack
KABOOM: Targeted AoE Attack
FREEM: Single Target or Cone attack that invokes a status effect as well as damage
Look at you mission status area, you may just have stumbled into a mission:
The game has “Open Missions” missions that are occurring over and over in a given geographic area. Once you enter that area, you get the mission and your share of the experience and rewards is based upon how much you contribute to the mission.