The table type may also affect which settings should be altered, but the following ones have the most influence on performance:
set-variable = read_buffer_size
set-variable = key_buffer_size
set-variable = max_allowed_packet
set-variable = table_cache
set-variable = sort_buffer
set-variable = net_buffer_length
set-variable = myisam_sort_buffer_size
4.5.6.4 SHOW VARIABLES section of MySql manual explains these settings in detail, but generally assigning higher values to these variables will increase the speed. But in case of such large tables, I would recommend to get additional memory (at least 512MB plus).