The Earth is built to last. It is a 4,550,000,000-year-old, 5,973,600,000,000,000,000,000-tonne ball of iron. It has taken more devastating asteroid hits in its lifetime than you've had hot dinners, and lo, it still orbits merrily. So my first piece of advice to you, dear would-be Earth-destroyer, is: do NOT think this will be easy.
This is not a guide for wusses whose aim is merely to wipe out humanity. I (Sam Hughes) can in no way guarantee the complete extinction of the human race via any of these methods, real or imaginary. Humanity is wily and resourceful, and many of the methods outlined below will take many years to even become available, let alone implement, by which time mankind may well have spread to other planets; indeed, other star systems. If total human genocide is your ultimate goal, you are reading the wrong document. There are far more efficient ways of doing this, many which are available and feasible RIGHT NOW. Nor is this a guide for those wanting to annihilate everything from single-celled life upwards, render Earth uninhabitable or simply conquer it. These are trivial goals in comparison.
This is a guide for those who do not want the Earth to be there anymore.
[thanks for the pointer to tbclone47]