In general, left-clicking will use whatever item you currently have selected. If you have a consumable selected, you'll consume it (assuming the cool down period isn't still in effect of course) and if you have a melee weapon selected you will swing that weapon, damaging everything in the area of affect. That part works exactly as you would expect for a 2D platformer.
However for just about every other item where the mouse pointer is when you left-click is usually very important. If you're swinging some kind of mining tool (pickaxe, axe, hammer, hamaxe) then it will only target the block your mouse pointer is on, regardless of what blocks the animation hits or doesn't hit. This means that you can mine at a range, albeit a limited one. You can also mine through obstructions. For all the placeable items it works pretty much the same way. The block or item will be placed at the location of the mouse cursor, assuming it's within the same limited range, regardless of any obstructions.
The progression through Minecraft is pretty clear. Minecraft is clearly an FPS game, except instead of guns you have tools (or your fists =) so it's immediately clear that if you want to affect a block you need to target it with the cross-hairs/mouse cursor. And like Terraria you can affect blocks at a limited distance, although in the case of Minecraft you need to have a clear line of sight.
Once you're used to that the jump to Terraria's system seems pretty intuitive, but apparently if you skip the middle step of Minecraft then it's not so obvious.
Oh, and a little stumbling block that both neonelephant and i encountered. When you first open up the crafting menu after creating a crafting table some of the first items in the list will be things like "dirt wall", "wood wall", "stone wall", etc. Those are not actually walls that will keep monsters out! They're just background panels for wallpapering your rooms! To build real walls you just place the original blocks of wood, dirt or stone that you mined. You don't need to do any crafting for that at all! (I have no idea why they don't just call then "Wood Panel", "Dirt Panel", etc in order to avoid the confusion.)