The general rule of thumb was to use InnoDB to write intensive tables (due to its row locking nature) and MyISAM for the read-heavy loads. I have seen a few very busy sites fully on InnoDB running without any hiccups or drop in performance too.
Drupal 7 defaults to InnoDB as the database abstraction layer has been rewritten and immensely improved.
You could look into MariaDB which is a drop-in replacement for MySQL, faster and has extra engines. There is also Percona, another high performance replacement. They both address some of the downsides of InnoDB.
The reason I am listing the alternatives is that Oracle made a few very suspicious moves and it may be that pretty soon we won't be able to use MySQL for free. (see http://arstechnica.com/business/news/2011/09/oracle-may-fork-itself-with-recent-mysql-moves.ars)
If bigger changes are not viable/possible, I'd recommend making a clone of the site using InnoDB and load test it using tools like Apache Benchmark, siege, New Relic