1) If you have lots of short connections and you want to tune the amount of time that the kernel will keep half-closed connections around then you can play around with changing the values of net.ipv4.tcp_fin_timeout, net.ipv4.tcp_tw_reuse, net.ipv4.tcp_tw_recycle, and net.ipv4.tcp_max_tw_buckets.
2) If you have a modern NIC then you probably need to tweak the txqueuelen in your ifconfig options.
3) If you are get hits from a large number of random browsers then sometimes setting net.ipv4.tcp_no_metrics_save and net.ipv4.tcp_moderate_rcvbuf to turn off cacheing of flow metrics helps.
4) Increase net.core.somaxconn to increase your listen queue size.
5) If you have a local firewall like iptables in place make sure you increase net.ipv4.ip_conntrack_max, direct your high-traffic ports to the NOTRACK table, and play around with all of the various net.ipv4.netfilter.ip_conntrack_tcp_timeout_* settings.