These are some settings values I look at when I start up a new MySQL instance. Not all instances of MySQL will have the same, so I tweak until I get optimal performance out of MySQL. Also remember not to go into swap when allocating memory.

General MySQL Settings
The Most important ones are:
Key Buffer
The key buffer holds the indexes of tables in memory and a bigger key buffer results in faster row lookups. Adjust according to your own needs. Bigger is better, but prevent swapping at all costs. A good rule of thumb seems to be to use 1/4 of system memory.

Query Cache
This is where the magic happens. Well, not magic really, just plain old caching. Keeping the result of queries in memory until they are invalidated by additional writes enhances performance by magnitudes. The query_cache_size, as the name suggests, is the total size of memory available to query caching. The value query_cache_limit is the maximum number of kilobytes one query may be in order to be cached. Setting this value too high might prevent a lot of smaller queries to be cached. Setting it too low will result in bigger queries to never be cached, and the smaller queries not being able to completely fill the cache size, which would be a waste of resources. Adjust according to your own needs and memory available:

Table Cache
An important variable if your application accesses many tables. It is the number of tables a thread can keep open at the same time. A value of 512 should do no harm.

Sort Buffers
sort_buffer_size (the variable previously known as sort_buffer), used for grouping and sorting and is a per-thread buffer. If the buffer can not hold the data to be sorted, a sort is performed on disk. Watch out for making this too large as the buffer is allocated for every thread that needs sorting and with many sorts it can easily consume all your memory.

Binary Logging
MySQL has a few powerful features. Replicating data changes to a second server is one of them. MySQL keeps a log file of data changes which is used for this purpose. If you do not use replication or use the file as incremental backup, you can disable it. This will save you expensive disk write actions for every change to your data. For applications that have a lot of frequently updated data, this can be quite a performance boost. According to the official docs, this will generally result in just a 1% boost but it’s an easy gain if you do not need the log. Read more about the binary log here. Comment the following line:
log-bin = /var/log/mysql/mysql-bin.log

Temporary Tables
Temporary tables are used for sorting and grouping. The buffer is created on demand so watch out for setting this too high here as well. If the buffer cannot accomodate the data, a temp file is used on disk instead.

Delayed Writing
This setting can greatly improve writing or updating data to a table. Instead of directly committing data to the disk, MySQL queues writes and returns write queries immediately. Be very very careful with this, because this also means that in case of a power failure or crash, you lose data. You can use this for logging if you don’t mind losing a couple of rows in case of a crash.

Connection Timeout
This is a little tweak that determines the closing of sleeping connections. The default is one hour and is often too long for practical purposes. I often set this at one minute instead (60).
wait_timeout = 60
The above settings are just to make mysql a little faster in general. You can get much better speed improvements by optimizing the database itself. Setting the correct indexes on tables can be a life-saver.

MySQL Innodb Settings
The most important ones are:

innodb_buffer_pool_size
70-80% of memory is a safe bet. I set it to 12G on 16GB box.

innodb_log_file_size
This depends on your recovery speed needs but 256M seems to be a good balance between reasonable recovery time and good performance

innodb_log_buffer_size=4M
4M is good for most cases unless you’re piping large blobs to Innodb in this case increase it a bit.

innodb_flush_log_at_trx_commit=2
If you’re not concern about ACID and can loose transactions for last second or two in case of full OS crash than set this value. It can dramatic effect especially on a lot of short write transactions.

innodb_thread_concurrency=8
Even with current Innodb Scalability Fixes having limited concurrency helps. The actual number may be higher or lower depending on your application and default which is 8 is decent start

innodb_flush_method=O_DIRECT
Avoid double buffering and reduce swap pressure, in most cases this setting improves performance. Though be careful if you do not have battery backed up RAID cache as when write IO may suffer.

innodb_file_per_table
If you do not have too many tables use this option, so you will not have uncontrolled innodb main tablespace growth which you can’t reclaim. This option was added in MySQL 4.1 and now stable enough to use.

Also check if your application can run in READ-COMMITED isolation mode – if it does – set it to be default as transaction-isolation=READ-COMMITTED. This option has some performance benefits, especially in locking in 5.0 and even more to come with MySQL 5.1 and row level replication.