Best practice for Exchange 2010 HA topology considering 6 x Exchange licenses and TMG 2010

That setup doesn't sound too ridiculous to me, and I wouldn't change much. I'm assuming all the preparatory work has been done (such as multiple Active Directory Sites, Domain controllers in each site etc.) so I won't go into great detail about that. If you can stretch your budget a little bit, I would tweak your CAS topology a little bit to eliminate the SPOF.

You can install the Hub Transport role on your Mailbox servers and they will automatically load balance themselves according to the Active Directory site they reside in. That's a quick and easy win, and I can't see that much of a reason not to do this.

If your budget can accomodate 2 hardware load balancers, you can also install the CAS role on the Mailbox servers as well. You'd then create A records in DNS for your load balancers and configuire the appropriate Mailbox Databases in each site to use the CAS Array for the site.
To do this, issue the command New-ClientAccessArray -Fqdn "ex-sitename-casarray.acme-widgets.com" -Site "AD-Site-MAIN" for each site (replacing your A records and real AD Site Names as appropriate).
Then issue Set-MailboxDatabase "<<Appropriate Database>>" -RpcClientAccessServer <<site-casarray-name.acme-widgets.com>> to make sure your Mailbox Databases use the CAS Array.

It is best to have a local copy of a users Mailbox in the same site as the user, so I would create 2 Mailbox Databases each replicating to a Mailbox server in the same site, as well as the other site (I've done a diagram to visualise it for you). For users in the MAIN site, home their Mailbox on the Main Mailbox DB and for users in the SUPPORT site, home their Mailboxes on the Support Mailbox DB.