I tried all kind of skills on my barbarian unlocking all the trees before I found out what I wanted to max. In my case it was 'dragon catcher' (as extra damage at the end of the combo and guard breaker) and 'triple strike' as a fast sweeping attack against hordes. My suggestion is that you take some time to experiment and find out which is the best single target combo you can pull out, and what skill actually works best when facing many enemies (it must be quick and high mobility, if you stand still you are gonna get killed). Once you find out which skills are good, you can invest in those as you level up. By the end of the game I was lv 60ish and I could max more then I was using to be honest. And there were some skills that I would have gladly skipped (such as Celestial Chop).

Once you take all the 3 different skills in a tree, you unlock an ultimate finishing move which, honestly, it's usually quite bad. The cool part is that they are cast by holding down parry and drawing simple symbols with the mouse (such as a line "-", or a "<", or a vertical line |, etc.). Way less cool is that my barbarian and his long sword made less damage with one of those ultimate then with a standard single target combo. For this reason, I would avoid investing into "attack power", which sounds like damage but it's just this ultimate charging stuff.

It goes without saying, you have to try to have the best jewels available on your weapon and armour slots. Weapon slots only grant offensive bonuses viceversa armour slots only grant defensive ones.
There is no equipment in this game! Your looks will change according to your jewel setup. As the game progress you will unlock up to 6 slots for your weapon and 6 for your armour.

Three identical jewels can be turned into a bigger one using the horadric cub.. emh... anyway, try to have perfect gems all over! You can always remove them and resocket them, but you cannot have more then one type of jewel on the same set (one per weapon and one per armour), so well you have to experiment and mix it up a bit, you might end up equipping both a perfect and a refined amethyst for instance.

Putting potions in the cube might result in jewels

Some vendor will start selling "uncut jade" at some point. 3 of those can be combined into a "refined jade", and 3 of those into a "perfect jade". Those jades can be turned one by one into the cube for random jewels - or crap if you are unlucky. Try to save for Perfect Jades, they can grant you special jewels (like Avarice, Lunar and Solar pearls) which are very powerful and can grant you higher bonuses. Your objective is to have these special powerful jewels along with a good selection of standard perfect jewels, so that you do not wear anything sub-optimal in your slots.
TIP: before transforming a Perfect Jade, Save and quit and make a copy of your local folder "SAVE". This way you can revert to this version in case your Perfect Jade turns into a crap. Perfect Jade = 3 Refined Jade = 9 Uncut Jade = 27000 gp. Some call it cheating, I call it less grinding.

There is something called Pavonine Agate (bascially impossible to find but somebody gives you one as a quest reward) that can be combined into the cube with another Jewel to create an Amulet. Amulet are jewels that grant all their bonuses all the time and you can carry up to 6 of them into a special bag! Use it on your best jewels... Great stuff!

There are some fights that are borderline frustrating in this game. You find yourself against a boss and other 5 enemies where you cannot land 3 hits in a row before being on the ground. Some general suggestions that helped me push through the difficult fights:

Try to activate and lure only a few enemies at the same time. Even in boss fights, it is usually possible to approach carefully and escape luring a few enemies at once. Repeat operations and clear before dueling the boss. When it is impossible to split and kite them, try with fast attacks, or stun them (such as Ground Shaker) before attacking. These are also the perfect occasions for making use of your ultimate skills and those consumables like decoy or summons.

Big Melee guy bosses are usually quite slow and you can parry or dodge all that they throw at you, just make sure to have space and clear the minions first.

King Hawk: this boss it's a flier. It is ridiculously difficult, my suggestion is to prepare yourself with an uppercut skill to hit him off guard and deliver your single target combo only when he is on ground (which is after he flies out of screen to plummet on you and grab you into a tornado - provided you manage to avoid him lol). Save lots of money and potions for this fights, the first time I met this guy I almost finished my gold :S

Wizard Wen: another flier, likes to one shot you into flames and other ridiculous aoes. Stay mobile, prepare with potions and use summons, as this boss likes to summon enemies as well

General Jo: last fight of the game, it is ridiculously difficult. I finished my gold, had to go back through act 3 to gather more gold and buy extra potions. This guy has a ridiculous amount of life, super strong attacks, it's hard to hit, and it is overall a basically impossible fight. The way I found to deal with him was to have two summons active, and attack with a shorter combo made on purpose once he was facing one of the summons. It took SO LONG.

My single target 14hit combo was made by: Attack x2, Triple Strike x2, Attack x2, Dragon Lift, Attack, Dragon Catcher.
In some parts of the game I used different quicker combos, for doing single target damage without being a target such as Attack x2, Triple Strike x3.
The shorter version of the single target combo that I used against Demon General Jo was: Triple Strike x2, Attack x2, Dragon Lift, Attack, Dragon Catcher. Engaging with Triple Strike allowed me to actually hit and deliver the rest, whereas starting with simple standard Attacks would be slower, more likely to be interrupted and less likely to stagger him enough for the rest of the combo to kick in.