"Top 3" because these are the most frequent. The rest in list 4 is just as frustrating though.
Mass Effect 2 (v 1.01) suffers 3 horrible bugs:
- Sudden airlift of Shepard (squad follows) with no escape. Under attack this makes Shepard an easy target, dead. Also stuck between crates with no way out. Only solution: reload savegame.
- Cover standup: during crossfire, Shepard when ducking for cover often stands up again! so you have to duck twice! The frequency differs per situation, at some places it never happens, sometimes it is 1 out of 10 but may also happen 4 out of 5 times. Under fire, when Shepard's health is almost lost > quickly duck > she stands up
> quickly duck again. Often she dies by standing up and receiving a fatal rocketblast right in her face. 
- Custom Female Shepard has no eyelids; only the lashes blink. It's a flaw in ... tion tool. This ruins her (otherwise superbly done) face.
- And a lot more Mass Effect 2 bugs that didn't make top 3, and other flaws
Cover standup:
during crossfire, Shepard when ducking for cover often stands up again! so you have to duck twice! The frequency differs per situation, at some places it never happens, sometimes it is 1 out of 10 but may also happen 4 out of 5 times. Under fire, when Shepard's health is almost lost > quickly duck > she stands up
> quickly duck again. Often she dies by standing up and receiving a fatal rocketblast right in her face. - Often when ducking Shepard to recover (Use Spacebar), she immediately stands up again even though i don't touch the Spacebar nor mouse!
I then have to make her quickly duck again before the reason for cover kills her! A few rockets aimed directly at Shepard... she stands up! Often she dies that way.
"Taking cover to regain health" behind a crate while being hunted by a giant Mech, she stands up again!
I know what i'm doing and i'm doing it right, but the game sabotages.
Each time you die that way in the final part of a battle -where saving is disabled- this means that you have to play the whole battle over again from most recent save before it! 
Like in Recruit Jack mission. A whole battle consisting of 3 sections: open door, do pickups, open next door, kill 1st series of blue sun troopers, quickly grab ammo and hide, kill 2nd series of blue sun troopers, quickly grab ammo and hide, kill 3d series of blue sun troopers plus a giant mech... die in the last section, restart from the beginning.
Mission to Secure Smuggled Cargo, behind the first rows of rocks: 4 out of 5 times.
Even more so in the first parts of the game, when Shepard hasn't got health upgrades yet, (when picking up some during a mission you can't implement them before getting back on the Normandy). So, with small health protection yourself but the enemies on hardcore strength, and this goddamned gameplay flaw where Shepard stands up instead of staying down to recover it can be a MAJOR torture to play through, as most of the playtime goes into repeating the same parts. You're dead before you know it just because Shepard stands up when she shouldn't. - Variation: Shepard refuses to duck behind a crate / bench / block, a belly-high glass fence.. No reaction to W+Spacebar. in the middle of being attacked, although said crate / bench / block / belly-high glass fence is "cover-supporting".
- Variation: Shepard refuses to vault over a crate / bench / block. No reaction to W+Spacebar, in the middle of being attacked, although said crate / bench / block is "vault-supporting".
Just enough health to vault over it and hide, but NO! Shepard doesn't recognize the Spacebar as order to vault. Dying that way is SO utterly stupid! I checked after having killed everybody: moving around goes quicker. Then returned to the same crate / bench / block and as a miracle suddenly vaulting was no problem!