How do I effectively use multiple skills?

You can assign function keys to individual skills. When the F key is pressed, that skill will become active.

To assign a function key to a skill:

1. Expand the skill switch menu by clicking your active skill
2. Hover your mouse over the skill you'd like to assign
3. Press the desired function key

This can be done for primary (left mouse button) and secondary (right mouse button) skills. An added benefit is that once the skills are assigned, you can use the mouse wheel to scroll through your secondary skills.

I would generally assign my alternate primary attacks to F1 and F2, damage dealers to F3-F6, buffs to F7-F9. This makes it easy to switch between primaries mid-fight with the F keys and secondaries with the mouse wheel. When I needed to buff: F7, cast, mouse-up, cast, mouse-up, cast, until all buffs are applied. Then back to F3.

Even I find that challenging. Controls in Diablo2 don't allow you to easily access your skills during an intense fight. Maybe it's there strategically !!

What I do is I use WSAD layout for my skills. Assign some of the best skills to easily accessible keys. For e.g My favorite is Barbarian. So I assign some skills that you need frequently during an intense fight to keys nearby. I assign double-swing to W. D tp whirlwind Space to leap etc. Some skills which cannot be used or are a bit slow to cast can be put on function keys or use mouse scroll on them

Regrettably, the control scheme is just that dated. You can't even give the same skill a key for each mouse button!

When I played Assassin, I liked to have my combo moves hotkeyed to right mouse and finishers to left mouse. This is because right click lets you "attack move" - if you click on the ground with a combo move, you will move towards it unless you are in melee with an enemy, in which case you will automatically attack the closest foe. If you want to use multiple combo moves, you can switch between them (with hotkeys) without lifting the mouse button. Once you have the charges you want, left-click on a suitable victim.

Of course, most assassins just play traps.

My personal favourite is using the scroll wheel for changing skills.

1. Scroll wheel up - previous skill.
2. Scroll wheel down - next skill.

Best setup I found was having three skills that you can alternate between extremely easily with your scroll wheel. If you picture something like this in your mind as you play you'll master the art of always scrolling in the right direction for the skill you want:

You are never more than one flick away from the skill you want. This also works with more skills however it gets a little more frustrating then in that you can end up casting the wrong spells often etc.