By chance, I happened to find the config wiki for mintty. It has a lot of great suggestions, one of which is how to set various options using escape sequences meant for xterm. So this works by not reading the config again but instead by interpreting escape sequences to override the existing color selections.

We can use this from URxvt by binding a key to a long chain of commands, each of which changes one of the 16 default colors.

For example, here I set alt+ctrl+l to change every color to C0C0C0:

# This stupidly changes every color to grey.
URxvt.keysym.M-C-l: command:\033]11;#C0C0C0\007\033]10;#C0C0C0\007\033]4;0;#C0C0C0\007\033]4;1;#C0C0C0\007\033]4;2;#C0C0C0\007\033]4;3;#C0C0C0\007\033]4;4;#C0C0C0\007\033]4;5;#C0C0C0\007\033]4;6;#C0C0C0\007\033]4;7;#C0C0C0\007\033]4;8;#C0C0C0\007\033]4;9;#C0C0C0\007\033]4;10;#C0C0C0\007\033]4;11;#C0C0C0\007\033]4;12;#C0C0C0\007\033]4;13;#C0C0C0\007\033]4;14;#C0C0C0\007\033]4;15;#C0C0C0\007

Perl Plugin

I have it "working" but not really, because it seems that there is a fundamental difference between resources defined as

URxvt.keysym.M-1: command:\033].......

and any attempt to do the same with $term->cmd_parse().

Is there anything that can be done about this? So far I have hardcoded entire light and dark color sets using (very long) escape sequences:

URxvt.keysym.M-C-l: command:\033]4;12;#72729F9FCFCF\007\033]4;1;#CCCC00000000\007\033]4;15;#EEEEEEEEECEC\007\033]4;14;#3434E2E2E2E2\007\033]4;5;#757550507B7B\007\033]4;3;#C4C4A0A00000\007\033]4;7;#D3D3D7D7CFCF\007\033]4;4;#34346565A4A4\007\033]4;10;#8A8AE2E23434\007\033]4;13;#ADAD7F7FA8A8\007\033]4;8;#555557575353\007\033]11;#FFFFFFFFFFFF\007\033]4;9;#EFEF29292929\007\033]4;2;#4E4E9A9A0606\007\033]4;0;#2E2E34343636\007\033]4;11;#FCFCE9E94F4F\007\033]10;#000000000000\007\033]4;6;#060698209A9A\007
URxvt.keysym.M-C-d: command:\033]4;12;#9090FF\007\033]4;1;#AA0000\007\033]4;15;#FFFFFF\007\033]4;14;#55FFFF\007\033]4;5;#AA00AA\007\033]4;3;#AA5500\007\033]4;7;#AAAAAA\007\033]4;10;#55FF55\007\033]4;13;#FF55FF\007\033]4;4;#0000AD\007\033]4;8;#555555\007\033]11;#000000\007\033]4;9;#FF5555\007\033]4;2;#00AA00\007\033]\007\033]4;0;#000000\007\033]4;11;#FFFF55\007\033]10;#00FF00\007\033]5;0;#00FF00\007\033]4;6;#00AAAA\007

This works exactly how I'd hoped it would and can be toggled at runtime so I'm marking this as answered, but why can't this be done dynamically from Perl? Here is what I have so far, I'm not a great Perl coder so please excuse the undoubtedly bad style.

Hopefully someone can chime in on what the issue is. This will be a nice plugin. Upstream is at github.

#! /usr/bin/env perl -w
# Author:  John Tyree
# Website: http://github.com/johntyree/urxvt-perls/blob/master/rotate-colors
# License: CCBYNC

# Use keyboard shortcuts to load colors of the form *.colorN:XXXXXX from a file
# This gives us "on demand" theme switching.

# Usage: put the following lines in your .Xdefaults/.Xresources:
#   URxvt.perl-ext-common: ...,rotate-colors
#   URxvt.colorFiles: ~/.Xresources,~/light.txt,~/dark.txt
#   URxvt.keysym.M-C-n:   perl:rotate-colors:forward
#   URxvt.keysym.M-C-p:   perl:rotate-colors:backward

use strict;


sub on_start {
    my ($self) = @_;
    $self->{current_index} = -1;
    my @arr = split(/,/, $self->x_resource('colorFiles') || '');
    $self->{color_files} = \@arr;
    ()
}

sub read_colors {
    my $fn = shift;
    open my $fin, $fn or print STDERR "Unable to open $fn for reading";
    my %colors;

    while (my $line = <$fin>) {
        if ($line =~ /(\w+)\s*:\s*(#[0-9a-fA-F]+)/) {
            $colors{$1} = $2;
        }
    }
    return %colors
}

sub escape_seq {
    my ($k, $v) = @_;
    my $cmd = "";
    if ($k =~ /^color(\d+)$/) {
        $cmd = "4;$1;$v";
    } elsif ($k =~ /^colorBD$/) {
        $cmd = "5;0;$v";
    } elsif ($k =~ /^colorUL$/) {
        $cmd = "5;1;$v";
    } elsif ($k =~ /^colorBL$/) {
        $cmd = "5;2;$v";
    } elsif ($k =~ /^colorRV$/) {
        $cmd = "5;3;$v";
    } elsif ($k =~ /^foreground$/) {
        $cmd = "10;$v";
    } elsif ($k =~ /^background$/) {
        $cmd = "11;$v";
    } elsif ($k =~ /^cursorColor$/) {
        $cmd = "12;$v";
    } elsif ($k =~ /^pointerColor$/) {
        $cmd = "13;$v";
    }
    return "\033]".$cmd."\007"
}

sub build_cmd {
    my $fn = shift;
    my %colors = read_colors($fn);
    my $s =  join("", map {escape_seq($_, $colors{$_})} keys %colors);
    return $s   # was implicit anyway
}

sub on_user_command {
    my ($self, $cmd) = @_;
    my @fs = @{$self->{color_files}};
    my $len = @fs;

    if ($cmd eq "rotate-colors:forward") {
        my $idx = $self->{current_index}++;
        my $fn = $fs[$idx % scalar(@fs)];
        $self->cmd_parse(build_cmd($fn));
    } elsif ($cmd eq "rotate-colors:backward") {
        my $idx = $self->{current_index}--;
        my $fn = $fs[$idx % scalar(@fs)];
        $self->cmd_parse(build_cmd($fn));
    }
    ()
}