I dont know much about 3D actually, but supposing you mean by 2D game, really a 2D game, and not a 2D game, that is actually using 3D graphics, then no.
Basically idea is that you have like two rectangle paper pieces, other one is player, and other one is enemy (naturally there can be many), then each time you move these paper pieces places on screen (this is how you get the movement in game), you will do so called collision check, which means that it is checking if these two paper pieces are touching each other. If they are, then happens collision, if not, then no collision.
and in practice this is usually (depending upon your choice of programming language) done about:
x = collision(playerpaperpiece, enemypaperpiece)
if x= TRUE, then goto collisionpartofprogram
Most likely, no need to be afraid of this thing.
There are some possibilities that you might need some more advanced methos for collision check, this would be for example if these paper pieces are moving so fast, that it is possible that player first shows on left side of the enemy paper piece, and on next sceenupdate it already shows on right side of enemy paper piece.
In this case simple check of collision, would results FALSE, athough in reality it should have happened, since that piece of paper cant get on other side of enemy, without going through it.
But these are quite rare. Basically if you have very small sized (like couple of pixels only) characters, of if there is possibility to move real fast (as example, mouse pointer)
To get the idea of the speed required, you can right now move your mouse pointer real fast and you can notice that it is drawn only to some of the places, when you slow down that movement a bit, you get pretty good idea about how fast these characters would really need to move before simple collision check wouldnt do anymore.
Naturally, if there are lots of stuff happening on screen and hence your game slows down to only 4 frames per second, then that is different matter again, and then it is much easier getting past collision check.