So by default iTerm2 uses whatever is the default browser, which I generally use Chrome for work related things, however I like to use Firefox for personal stuff. I had to look around for a while to find this since I am not an OSX person really, figured someone else will find it useful.
Go to Preferences > Profiles > Advanced > and in the Smart Selection area hit Edit.
Select HTTP URL and hit the Edit Actions button
Add the following entry:
Title: Open in Firefox
Action: Run Command
Parameter: open -a Firefox \0
Hit OK and you should be good to go, now if you hold ⌘ and click on a link (say within Weechat) it will kick it over to Firefox specifically.