pecl/xhprof extension in php.ini
extension=xhprof.so
xhprof.output_dir=/tmp
xhprof vhost
<VirtualHost *:80>
  ServerName xhprof.localhost
  UseCanonicalName Off
  DocumentRoot /var/www/xhprof
  ErrorLog /var/log/apache2/xhprof-error.log
  CustomLog /var/log/apache2/xhprof-access.log combined
  DirectoryIndex index.php index.html
</VirtualHost>
enable xhprof for a vhost
# For XHPROF Profiling
  php_value auto_prepend_file /var/www/xhprof/header.php
  php_value auto_append_file /var/www/xhprof/footer.php
...
header.php
<?php
include '/var/www/xhprof/xhprof_lib/utils/xhprof_lib.php';
include '/var/www/xhprof/xhprof_lib/utils/xhprof_runs.php';
xhprof_enable(XHPROF_FLAGS_CPU + XHPROF_FLAGS_MEMORY);
footer.php
<?php
$app = $_SERVER['HTTP_HOST'];
$xhprof_data = xhprof_disable();
$xhprof_runs = new XHProfRuns_Default();
$id = $xhprof_runs->save_run($xhprof_data, $app);
$ua = urlencode($app);
$profiler_url = "http://xhprof.localhost/index.php?run=$id&source=$ua";
echo '<a href="'. $profiler_url .'" target="_blank">Profiler output</a>';
Now hit the server a few times to warm up the caches, then click the "Profiler Output" link at the bottom.

mysql_connect and mysql_set_charset
--- wp-db.php	(revision 13595)
+++ wp-db.php	(working copy)
@@ -499,7 +499,7 @@
-		$this->dbh = @mysql_connect( $dbhost, $dbuser, $dbpassword, true );
+		$this->dbh = mysql_pconnect( $dbhost, $dbuser, $dbpassword );
@@ -518,7 +516,7 @@
-				mysql_set_charset( $this->charset, $this->dbh );
+#				mysql_set_charset( $this->charset, $this->dbh );
And as we are browsing the source code, we can replace most time() calls with $_SERVER['REQUEST_TIME'] and also any date() or gmdate() calls that don't already have a timestamp argument, we can add $_SERVER['REQUEST_TIME'] to those.

$_SERVER['REQUEST_TIME'] example
--- ./load.php	2010-03-05 09:31:16.573829617 -0800
+++ ../../wp2/wp-includes/load.php	2010-03-05 16:57:13.452580398 -0800
@@ -138,7 +138,7 @@
-	if ( ( time() - $upgrading ) >= 600 )
+	if ( ( $_SERVER['REQUEST_TIME'] - $upgrading ) >= 600 )
Optimize is_serialized
<?php
   ...
   // This condition gets hit often:
   if ( !preg_match( '/^([adObis]):/', $data, $badions ) )
      return false;
Faster alternative using strpbrk
<?php
if(strlen($data)>1 && strpbrk($data,'adObis')==$data && $data[1]==':') $badions[1] = $data[0]; 
else return false;
And finally, let's disable the phone-home version update check and the cron functionality. We can do these out-of-band ourselves.

Disable cron and update check
...
Index: wp-settings.php
===================================================================
--- wp-settings.php	(revision 13594)
+++ wp-settings.php	(working copy)
@@ -118,11 +117,11 @@
 require( ABSPATH . WPINC . '/bookmark.php' );
 require( ABSPATH . WPINC . '/bookmark-template.php' );
 require( ABSPATH . WPINC . '/kses.php' );
-require( ABSPATH . WPINC . '/cron.php' );
+#require( ABSPATH . WPINC . '/cron.php' );
 require( ABSPATH . WPINC . '/deprecated.php' );
 require( ABSPATH . WPINC . '/script-loader.php' );
 require( ABSPATH . WPINC . '/taxonomy.php' );
-require( ABSPATH . WPINC . '/update.php' );
+#require( ABSPATH . WPINC . '/update.php' );
 require( ABSPATH . WPINC . '/canonical.php' );
 require( ABSPATH . WPINC . '/shortcodes.php' );
 require( ABSPATH . WPINC . '/media.php' );

Index: default-filters.php
===================================================================
--- default-filters.php	(revision 13595)
+++ default-filters.php	(working copy)
@@ -198,8 +198,8 @@
 }
 
 // WP Cron
-if ( !defined( 'DOING_CRON' ) )
-	add_action( 'sanitize_comment_cookies', 'wp_cron' );
+#if ( !defined( 'DOING_CRON' ) )
+#	add_action( 'sanitize_comment_cookies', 'wp_cron' );