24x7x365 high-volume ops ideas

I have a few high-volume, fairly large clusters that I'm struggling to keep
up 24x7x365.  I want to ask for advice from anyone with similar experience
or hard-won wisdom.

Generally these are clusters with 100-200 queries/second, maybe 10GB-30GB of
data (always increasing), and maybe 10% writes.  A little regular routine
downtime for maintenance would do wonders for these systems, but
unfortunately, the requirement is 100% uptime all the time, and any
downtime at all is a liability.  Here are some of the issues:

1)  Big tables.  When the tables grow large enough, it takes too long to
vacuum them.  In some cases there's just too much data.  In other cases,
it's dead space, but both reindex and vacuum full block production queries
(a lesser version of downtime).  In the past, we have taken a PR hit for
downtime to dump/reload (we've found it to be faster than vacuum full).
Async replication helps with cluster moves from one server to another, but
still don't have a low-to-zero downtime solution for regular maint.

2)  Big tables, part 2.  Of course, customers want all data that ever
existed online and quickly available via sub-second queries.  I assume at
some point this data is going to be too much for one table (how much is too
much?).  This is a little vague, I know, but what sorts of segmenting
strategies to folks employ to deal with data that cannot be retired but
gets too expensive to vacuum, etc.

3)  Simple restarts for configuration changes (shared_buffers,
max_connections, etc).  When we have to break client connections, we have
to notify the customer and take a PR hit.  Maybe pgpool is a possible
solution?

Are these issues for Oracle, DB2, etc as well?

TIA.

Ed