To access and change graphics options (fullscreen mode, resolution, etc), you first have to create a new world, then go into the new menu and click on the Graphics tab at the top.

In your tool hotbar on the bottom of the screen there is two highlighted boxes, white and yellow. These boxes allow you to select an item and put it into one of your two hands.
To select and use an item with your right hand, use the scroll wheel on your mouse to move the white box.
To use your left, hold down the Shift key while using the scroll wheel.

Right click on the ground or any surface to use the item that is selected in your left hand.
Left click to use the item in your left hand.

To craft an item, you must first harvest materials. Use your pickaxe to chop wood from a tree.
Once you have materials, use the U key to open up the crafting interface.
You have the ability to manually place items into the top 2x2 grid, or you can press the C key to open easy craft, which lets you see all of your craftable options.
When you have the necessary materials, easy craft lets you easily craft those materials into a something.
To craft more complex items, create a workbench with four wood blocks. This unlocks more crafting space for more materials.

To view all of your items and armor slots, press the I key to open up your inventory (I for inventory, neat). This interface allows you to put items into your hotbar and to put armor on.

To enter creative mode, create a new world and select creative (I don't think you can switch a survival world into creative).

First off, to fly, all you have to do is press the F key. Use space to fly up and crtl to fly down. Press F again to fly faster, and press F again to stop flying.

To access unlimited tools and blocks, press the B key. This opens up a shop-menu-like interface where you can click either the Item or Blocks tabs to access the tab's subtabs.

There is a total of 16 skills. To gain XP to raise a skill, perform tasks related to that skill.
To view your skills, press the ESCAPE key, then click on the tab above that says 'Character', then click on the menu item which says 'Skills'. (This character tab also lets you change your avatar.)

Thanks to www.totalminer.wikia.com/wiki/Player_Skills for most information

Health - Determines your maximun hit points (health)
Your max HP starts at 10, +3 max HP points gained per level.
To gain XP, attack anything with a health bar, including hostile and passive mobs.

Strength- Increases attack damage; mining, chopping, and digging speed; and allows you to use claymores.
To gain XP, you can basically do anything, such as attacking, mining, building, farming, etc.

Attack - Improves ability to fight with most melee weapons (not bows)
Increases chance to hit in melee combat and allows you to use better quality melee weapons.
To gain XP, attack enemies with swords and battle axes.
Defence - Helps you defend yourself, and to better fight using spears
Increases chance to block attacks and allows you to use better quality spears, armor, and shields.
To gain XP, attack enemies with your spear.

Ranged - Improves ability to fight with ranged weapons such as bows and the grenade launcher
Increases chance to hit in ranged combat and allows you to use better ranged weapons and ammunition.
To gain XP, attack enemies with ranged weapons.

Mining - increases your ability to use pickaxes, your mining speed, allows you to use better quality pickaxes and to mine more types of blocks.
To gain XP, mine blocks using a pickaxe.

Digging - Improves your ability to use shovels, your digging speed, better quality shovels, and to dig more types of blocks.
To gain XP, dig blocks using a shovel.

Chopping- Improves your ability to use hatchets, increases chopping speed, and allows you to use better quaity hatchets and to chop more types of blocks.
To gain XP, chop blocks using a hatchet.

Building - Improves building ability, increases block placement speed, and allows you to place more types of blocks.
To gain XP, place blocks in the world.
Crafting - Improves ability to craft items and leather armor, and allows you to use more crafting recipes at a workbench.
To gain XP, craft specific items a workbench such as blocks, items, power, decor, jewelry, and leather armor.

Smithing - Improves ability to smith tools, weapons, most armors, and allows you to use more smithing recipes at a workbench.
To gain XP, smith certain items such as tools, weapons, and most armor.

Farming - Improves your ability to farm; increases tilling, planting, and harvesting speed; allows you to use better quality hoes and scythes, and allows you to plant more types of seeds.
To gain XP, you must till land, plant seeds, and use a scythe to harvest crops.

Cooking - Improves ability to cook food at a workbench or furnace, increases speed at which food cooks, allows you use more cooking recipes at a workbench, and allows you to cook more food items in a furnace.
To gain XP, cook certain items at a workbench and cook food items in a furnace.

Looting - Improves ability to loot mobs and chests, causes slain mobs and treasure chests to drop and spawn better items.
To gain XP, pick up mob drops and open pre-generated underground treasure chests.