Disk Drive Partition: Single vs Multiple
If you are comfortable using Terminal.app, I recommend multiple partitions.

Moving Home

These questions explain how to move a user account to a separate partition:


Is there a safe way to move the /Users folder to a separate volume/drive?
How to make the Users Directory a different partition in Snow Leopard?


Considerations, Benefits, and Choices

Hardware

It is difficult to justify the choice based solely on the impact to the storage hardware.

If the same content is spread across one or more partitions – but always on a single physical drive – then the hardware impact is largely be irrelevant.

Roughly the same number of read and writes will be performed on the physical drive either way.

Software

From a software perspective, there are benefits to separating mostly static content from your frequently changing content.

OS X and your applications will largely remain static. They will be read many times but rarely changed.

Your user files will be likely be read and written frequently.

Applications

Well behaved applications will continue to just work. A consumer Mac application that requires a single partition should be considered faulty.

Some applications will write content within the /Library/ folder on the OS X partition. This content is likely to be caches and content shared across multiple users. It should never be content specific to a single user.

Smarter Back Ups

With separate partitions, you could choose to only back up your user files with Time Machine. If you back up drive is small, you could choose not to back up OS X and your applications.

In case of a disaster, your own files would be safe but you would need to download and re-install OS X. Services like BackBlaze take this approach; only user files are backed up.

Easier Clean Updates

As a developer, I have OS X on a separate partition to my files. This has historically made it easier to test with multiple versions of OS X. It has made blanking and re-installing a clean copy of OS X possible.

Encryption / FileVault2

You can choose to encrypt all, some, one, or none of the partitions using the full disk encryption built-into OS X, FileVault.

If you only have one partition, the choice becomes encrypting nothing or everything.

Create a Fallback User

If you decide to move your user area off the OS X partition, I recommend creating a second administrator user account on the OS X partition. This back up account will be useful in case of future problems. If your other partitions do not mount, or you need to demonstrate the computer works but without decrypting your personal files, this fallback administrator account can be helpful.

The "Right" Partition Sizes

The difficult choice to make with multiple partitions, is how large each partition should be? This will depend on your applications.

In general try and leave 10 – 20% of your OS X partition free. This will allow for caches and other temporary files to be created, grow, and shrink while the computer is running.

An approach might be to determine how much you can safely back up and version. Then pick sizes based around that figure. Better to live frugally but be well backed up, than risk losing irreplaceable personal files.