If your purpose is to search against a protein database, you can hardly find anything better than ggsearch. Ggsearch is based on SSE2 and was written by Michael Farrar who developed the original striped SSE2-SW algorithm. It is the only open-source global aligner so far as I know.

Another notable implementation is swat from phrap. It does global alignment as well. Swat is probably the fastest (or very close to the fastest) SW/NW aligner without SIMD, but it may be tens of times slower than ggsearch.

A problem with needle, if I am right, is that it always fills the trace-back matrix and is thus not suitable search against a protein database. I believe ggsearch and swat compute the score first and only fill the trace-back matrix when they think the alignment score is high enough.

ggsearch36 does use sse2 instructions, but it also achieves a speed-up by not considering for alignment library sequences that are 25% shorter or 33% longer than the query.

There is also exonerate, which is quite mature and supports a variety of alignment models and heuristics.

You can look at:

• Global Pairwise Alignment Tools
• A previous BioStar post mentioned MUMmer

Marcin Cieślik and I wrote this module for python.

This is surely not as fast as anything that uses SSE, but it uses Cython/C so it's has pretty good performance.